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Background. To analyze the efficacy of various fractionation schedules for the palliation of head and neck cancer with radiation therapy. Methods. Sixty patients completed palliative irradiation to primary head and neck sites. The most commonly used fractionation regimen was the one previously described by the Radiation Therapy Oncology Group (RTOG) protocol 85-02 and was designed to deliver 440 cGy using 370 cGy fractionation, administered twice a day for 2 consecutive days at 2- to 3-week intervals for 3 total cycles. Results. The rates of palliative response were 83%, 77%, 67%, 86%, and 60% among those treated using the RTOG regimen, 7000 cGy/35 fractions, 3000 cGy/10 fractions, 3750 cGy/15 fractions, and 2000 cGy/5 fractions, respectively (p = .42). Nine percent (2/23) of those treated with the RTOG regimen developed grade 3+ toxicity compared with 37% among those treated with other schedules (p = .01). Conclusion. Although all of the analyzed schedules were effective at providing palliation, the RTOG 85-02 regimen was associated with less toxicity. © 2008 Wiley Periodicals, Inc. Head Neck, 2008

Straume, T., Amundson, S. A., Blakely, W. F., Burns, F. J., Chen, A., Dainiak, N., Franklin, S., Leary, J. A., Loftus, D. J., Morgan, W. F., Pellmar, T. C., Stolc, V., Turteltaub, K. W., Vaughan, A. T., Vijayakumar, S. and Wyrobek, A. J. NASA Radiation Biomarker Workshop. September 27–28, 2007. Radiat. Res. 170, 393–405 (2008). A summary is provided of presentations and discussions at the NASA Radiation Biomarker Workshop held September 27–28, 2007 at NASA Ames Research Center in Mountain View, CA. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including those exposed during long-duration space travel. Topics discussed included the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose ...

BACKGROUND. The purpose of the current study was to determine the incidence of late recurrences, which were defined as those occurring ≥5 years after initial therapy, among patients treated for salivary gland cancer. METHODS. Between 1960 and 2000, 145 patients underwent definitive therapy for localized carcinomas of the salivary glands and were clinically without evidence of disease at 5 years of follow-up. Cumulative probabilities for developing a subsequent late recurrence were estimated using the Kaplan-Meier method. RESULTS. The 10-year and 15-year cumulative probabilities of late recurrence in patients who were free of disease at 5 years were 13% and 18%, respectively. The crude rates of late recurrence by histologic subtype were adenoid cystic carcinoma (26%), mixed malignant tumor (25%), mucoepidermoid carcinoma (17%), adenocarcinoma (10%), and acinic cell carcinoma (8%). Sites of late recurrence included distant metastasis (17 patients), local recurrence (8 patients), and regional recurrence (2 patients). The median time to late recurrence was 7.1 years (range, 5.2–23.1 years) from the date of initial surgery. Salvage treatment varied according to location of disease recurrence and initial treatment characteristics. The 15-year estimate of overall survival was 39% for patients who experienced a late recurrence compared with 71% for those who remained free of disease (P = .001). CONCLUSIONS. A significant proportion of patients who are presumed to be cured of their disease at 5 years after initial treatment for salivary gland cancer will be found to develop late disease recurrence with additional follow-up. Cancer 2008. © 2007 American Cancer Society.

Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

Purpose: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. Methods and Materials: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%), and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5–18.7 years). Results: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3–4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. Conclusion: Lymph node metastasis, high tumor grade, positive margins, and T3–4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.

Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3–267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively ( p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% ( p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.

Purpose: To review a single-institutional experience with the use of intraoperative radiation therapy (IORT) for recurrent head-and-neck cancer. Methods and Materials: Between 1991 and 2004, 137 patients were treated with gross total resection and IORT for recurrence or persistence of locoregional cancer of the head and neck. One hundred and thirteen patients (83%) had previously received external beam radiation as a component of definitive therapy. Ninety-four patients (69%) had squamous cell histology. Final surgical margins were microscopically positive in 56 patients (41%). IORT was delivered using either a modified linear accelerator or a mobile electron unit and was administered as a single fraction to a median dose of 15 Gy (range, 10‐18 Gy). Median follow-up among surviving patients was 41 months (range, 3‐122 months). Results: The 1-year, 2-year, and 3-year estimates of in-field control after salvage surgery and IORT were 70%, 64%, and 61%, respectively. Positive margins at the time of IORT predicted for in-field failure (p 0.001). The 3-year rates of locoregional control, distant metastasis-free survival, and overall survival were 51%, 46%, and 36%, respectively. There were no perioperative fatalities. Complications included wound infection (4 patients), orocutaneous fistula (2 patients), flap necrosis (1 patient), trismus (1 patient), and neuropathy (1 patient). Conclusions: Intraoperative RT results in effective disease control with acceptable toxicity and should be considered for selected patients with recurrent or persistent cancers of the head and neck. © 2007 Elsevier Inc. Intraoperative radiation, Head and neck, Cancer.

Background. The optimal treatment for patients with locally recurrent carcinomas of the salivary glands is unclear. Methods. Ninety-nine patients underwent salvage surgery for locally recurrent salivary gland carcinomas. Eighty-one (82%) had previously received radiation. Thirty-seven patients (37%) received intraoperative radiation therapy (IORT) to a median dose of 15 Gy (range, 12–18 Gy) at the time of salvage. Results. The 1-, 3-, and 5-year estimates of local control after salvage surgery were 88%, 75%, and 69%, respectively. A Cox proportional hazard model identified positive margins (0.01) and the omission of IORT (p = .001) as independent predictors of local failure. The 5-year overall survival was 34%. Distant metastasis was the most common site of subsequent failure, occurring in 42% of patients. Conclusions. IORT significantly improves disease control for patients with locally recurrent carcinomas of the salivary glands. The high rate of distant metastasis emphasizes the need for effective systemic therapies. © 2007 Wiley Periodicals, Inc. Head Neck, 2008

Background Stereotactic body radiation therapy (SBRT) has emerged as a standard treatment of early-stage, medically inoperable lung cancer. Limited data have evaluated the radiation pneumonitis (RP) risk with SBRT after previous anatomic lung resection (ALR). We assessed the incidence of RP and all pulmonary toxicity (PT) in patients who underwent lung SBRT after ALR and compared them with those of patients without previous ALR. Materials and Methods We reviewed the medical records of 84 consecutively treated patients with stage T1-T2b non–small-cell lung cancer (NSCLC) treated with 88 courses of SBRT for 94 lung tumors from January 2007 to December 2014, including 17 patients with previous ALR. The rates of RP and all PT were compared between the patients with and without previous ALR. Results At a median follow-up duration of 18.3 months (range, 1.8-85.6 months), the crude grade 2+ RP rate was 5.9% and 2.8% for patients with and without previous ALR, respectively ( P = .51). The corresponding 2-year estimates of freedom from RP were 89% and 97% ( P = .51). The crude rate of all grade 2+ PT was 11.8% and 2.8% for those with and without previous ALR ( P = .11), with 2-year estimates of freedom from PT of 97% and 84% ( P = .11), respectively. The 2 cohorts were well matched by the mean lung dose, percentage of lung volume receiving 20 Gy ( P = .86), and prescribed dose ( P = .75). The 2-year estimates of local control, cause-specific survival, and overall survival were similar between the 2 cohorts. Conclusion The observed rates of PT were low among all patients, with a trend toward increased grade 2 and 3 lung toxicity among patients with previous ALR. Previous ALR did not increase the risk of grade 4 and 5 RP, and SBRT appears safe and effective in this population.

Recent improvements in toxicity profiles of pediatric oncology patients are attributable, in part, to advances in the field of radiation oncology such as intensity modulated radiation (IMRT) and proton therapy (IMPT). While IMRT and IMPT deliver highly conformal dose to targeted volumes, they commonly demand the addition of 2- or 3-dimensional imaging for precise positioning--a technique known as image guided radiation therapy (IGRT). In this manuscript we address strategies to further minimize exposure risk in children by reducing effective IGRT dose. Portal X rays and cone beam computed tomography (CBCT) are commonly used to verify patient position during IGRT and, because their relative radiation exposure is far less than the radiation absorbed from therapeutic treatment beams, their sometimes significant contribution to cumulative risk can be easily overlooked. Optimizing the conformality of IMRT/IMPT while simultaneously ignoring IGRT dose may result in organs at risk being exposed to a greater proportion of radiation from IGRT than from therapeutic beams. Over a treatment course, cumulative central-axis CBCT effective dose can approach or supersede the amount of radiation absorbed from a single treatment fraction, a theoretical increase of 3% to 5% in mutagenic risk. In select scenarios, this may result in the underprediction of acute and late toxicity risk (such as azoospermia, ovarian dysfunction, or increased lifetime mutagenic risk) in radiation-sensitive organs and patients. Although dependent on variables such as patient age, gender, weight, body habitus, anatomic location, and dose-toxicity thresholds, modifying IGRT use and acquisition parameters such as frequency, imaging modality, beam energy, current, voltage, rotational degree, collimation, field size, reconstruction algorithm, and documentation can reduce exposure, avoid unnecessary toxicity, and achieve doses as low as reasonably achievable, promoting a culture and practice of "gentle IGRT."

Importance There is no consensus whether primary surgery followed by either adjuvant radiotherapy (RT) or adjuvant chemoradiation (CRT) or definitive CRT should be the standard treatment approach to advanced-stage hypopharyngeal squamous cell carcinoma (HP SCC). Objectives To determine survival outcomes for patients with advanced-stage HP SCC treated at a single institution with either primary surgery plus RT or CRT or definitive CRT. Evidence and Data Acquisition We conducted a retrospective analysis of prospectively collected medical records in an institutional database for patients with HP SCC newly diagnosed between January 1999 and April 2013. Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between treatment groups using the Kaplan-Meier method, with multivariate Cox regression analysis used to control for demographic and clinicopathologic features. Results We identified 166 consecutively treated patients, 90 of whom did not meet study criteria. Of the 76 included patients, 48 (63%) had undergone definitive CRT, and 28 (37%) had undergone primary surgery with adjuvant RT or CRT. The groups were well balanced by age, smoking history, and alcohol use. Five-year OS and RFS for patients treated surgically were 66.3% and 53.6%, respectively; for patients treated with definitive CRT, OS and RFS were 41.3% and 34.5%, respectively. Multivariate Cox regression analysis showed that surgical management was associated with clinically improved OS (hazard ratio [HR], 4.78; 95% CI, 0.91-25.03; P = .06) and RFS (HR, 2.97; 95% CI, 0.76-11.53; P = .12), although the difference was not statistically significant. Conclusions and Relevance Patients with advanced-stage HP SCC treated surgically with adjuvant RT or CRT showed a trend toward clinically improved OS and RFS compared with patients treated with definitive CRT. However, the difference was not statistically significant, and further investigation with larger controlled trials using modern approaches should be undertaken to optimize the initial management of advanced-stage HP SCC.

Purpose: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. Methods and Materials: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54–71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7–267 months). Results: The 5- and 10-year rate estimates of local control were 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease ( p = 0.0001), perineural invasion ( p = 0.008), omission of postoperative radiation ( p = 0.007), and major nerve involvement ( p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy ( p = 0.0004), T4 disease ( p = 0.005), and major nerve involvement ( p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. Conclusion: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.

The possible reemergence of smallpox through bioterrorism requires the preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre-event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain that has been safely used in over 50,000 persons. Until now, efficacy of this vaccine was unproven. Using two animal models, we show that LC16m8 and Dryvax elicit comparable humoral immune responses after a single vaccination and equivalently protect against lethal poxvirus disease. Thus, LC16m8 shows promise as a safe and effective smallpox vaccine with the potential for replacing Dryvax.

BACKGROUND The appropriate selection criteria for breast-conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision-making for patients treated by this multimodality approach. METHODS From a group of 340 patients treated with BCT after neoadjuvant chemotherapy, the authors previously determined 4 statistically significant predictors of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR): clinical N2 or N3 disease, residual pathologic tumor size > than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The M. D. Anderson Prognostic Index (MDAPI) was developed by assigning scores of 0 (favorable) or 1 (unfavorable) for each of these 4 variables and using the total to give an overall MDAPI score of 0–4. RESULTS The MDAPI stratified the 340 patients into 3 subsets with statistically different levels of risk for IBTR and LRR after neoadjuvant chemotherapy and BCT. Actuarial 5-year IBTR-free survival rates were 97%, 88%, and 82% for patients in the low (MDAPI overall score 0 or 1, n = 276), intermediate (MDAPI score 2, n = 43), and high (MDAPI score 3 or 4, n = 12) risk groups, respectively (P < 0.001). Corresponding actuarial 5-year LRR-free survival rates were 94%, 83%, and 58%, respectively (P < 0.001). CONCLUSIONS Patients with an MDAPI score of 0 or 1, which made up 81% of the study population, had very low rates of IBTR and LRR. The MDAPI enabled the identification of a small group (4%) of patients who are at high risk for IBTR and LRR and who may benefit from alternative locoregional treatment strategies. Cancer 2005. © 2005 American Cancer Society.

Purpose: To show the first in-human Megavoltage (MV)-Topogram acquisition for the evaluation of the potential for MV-Topogram-based alignment as an alternative to MVCT for reducing dose and imaging time. Methods: A lung cancer patient was enrolled in an ongoing IRB-approved clinical trial at our institute. The patient was set up using the clinical protocol employing positioning lasers. 3.2mm diameter tungsten spheres were placed on the patient's skin at their alignment tattoos to check surface-based marker concordance between topograms and MVCT. Anterior-Posterior (AP) and lateral (LAT) MV-Topograms were acquired using gantry angles of 0°/90° with a 1mm collimator opening, all MLC leafs open, 4cm/s couch speed, and 12.5s scanning time. The topogram acquisition was immediately followed by the normal MVCT scan acquisition. MV-Topograms were reconstructed from the detector exit-data using in-house developed software. The topograms were also enhanced using contrast-limited adaptive histogram equalization (CLAHE). The MV-Topograms were registered to reference kV-based digitally reconstructed topograms. The localization results were compared against results obtained comparing the clinical MVCT to the kVCT simulation. Results: The shifts using the unenhanced Topograms, enhanced Topograms, and MVCT were (LAT, LONG, VERT, ROLL) (5.8mm, 2.6mm, −5.6mm, 0.34°), (3.9mm, 2.5mm, −2.2mm, 0.65°) and (2.4mm, 1.5mm, −3.0mm, 0.5°), respectively. The magnitude alignment differences between the enhanced Topograms and MVCT were within 1.5 mm and 0.15°. The average MVCT and total Topogram acquisition times were 272.9s ± 31.5s and 46s, respectively. Conclusion: MV-Topograms have the potential for providing equivalent performance with less dose and acquisition time than the traditional MVCT technique. We are evaluating other sites as well as adding patients to develop statistically significant analyses regarding the alignment quality differences. MV-Topograms are likely to be most clinically useful for bony anatomy and radiopaque marker-based alignments. The study was supported by an Accuray Grant.

To evaluate the incidence of locally recurrent breast cancer in patients treated with breast conservation surgery and radiation therapy to determine if increased local recurrence is observed in women examined by means of stereotactic core-needle biopsy (SCNB).Records of 551 consecutive patients with breast cancer who were treated with conservation surgery and radiation therapy were reviewed retrospectively. The 551 cases were divided into three groups: those examined by means of SCNB (n = 86), those examined by means of excisional biopsy preceded by needle localization (n = 242), and those in which the masses were palpable and who underwent biopsy without imaging guidance (n = 223). The local recurrence rate and the Mantel-Haenszel statistic for survival curves were calculated for each group. To test for statistical significance, chi(2) analysis was performed for categorical variables and a t test or analysis of variance was performed for calculation of continuous variables.With a mean follow-up of 4.9 years (range, 2.0-8.9 years), tumor recurrence rate in the SCNB group was 2.3% (two of 86), resulting in a 5-year actuarial recurrence-free rate of 0.96 +/- 0.03. For the needle-localized biopsy group, recurrence rate was 5.4% (13 of 242), with a 5-year actuarial tumor recurrence-free rate of 0.88 +/- 0.03. For the non-image-guided biopsy group, the recurrence rate was 10.3% (23 of 223), with a 5-year actuarial recurrence-free rate of 0.84 +/- 0.03. These rates were not significantly different when the SCNB group was compared with the needle-localized biopsy group. However, the recurrence-free rate was significantly greater for the SCNB group than that for the non-image-guided biopsy group (P =.03).In the present series to date, cancers diagnosed by means of SCNB were not associated with an increased incidence of local recurrence after breast conservation surgery and radiation therapy.

Importance There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment. Objectives To examine whether the Kirsten rat sarcoma viral oncogene homolog ( KRAS ) – variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS -variant with p16 status and blood-based transforming growth factor β1 (TGF-β1). Design, Setting, and Participants A total of 891 patients with advanced HNSCC from a phase 3 trial of cisplatin plus radiotherapy with or without cetuximab (NRG Oncology RTOG 0522) were included in this study, and 413 patients with available samples were genotyped for the KRAS -variant. Genomic DNA was tested for the KRAS -variant in a CLIA-certified laboratory. Correlation of the KRAS -variant, p16 positivity, outcome, and TGF-β1 levels was evaluated. Hazard ratios (HRs) were estimated with the Cox proportional hazards model. Main Outcomes and Measures The correlation of KRAS -variant status with cetuximab response and outcome, p16 status, and plasma TGF-β1 levels was tested. Results Of 891 patients eligible for protocol analyses (786 male [88.2%], 105 [11.2%] female, 810 white [90.9%], 81 nonwhite [9.1%]), 413 had biological samples for KRAS -variant testing, and 376 had plasma samples for TGF-β1 measurement. Seventy patients (16.9%) had the KRAS -variant. Overall, for patients with the KRAS -variant, cetuximab improved both progression-free survival (PFS) for the first year (HR, 0.31; 95% CI, 0.10-0.94; P = .04) and overall survival (OS) in years 1 to 2 (HR, 0.19; 95% CI, 0.04-0.86; P = .03). There was a significant interaction of the KRAS -variant with p16 status for PFS in patients treated without cetuximab. The p16-positive patients with the KRAS -variant treated without cetuximab had worse PFS than patients without the KRAS -variant (HR, 2.59; 95% CI, 0.91-7.33; P = .07). There was a significant 3-way interaction among the KRAS -variant, p16 status, and treatment for OS (HR, for KRAS -variant, cetuximab and p16 positive, 0.22; 95% CI, 0.03-1.66; HR for KRAS -variant, cetuximab and p16 negative, 1.43; 95% CI, 0.48-4.26; HR for KRAS -variant, no cetuximab and p16 positive, 2.48; 95% CI, 0.64-9.65; and HR for KRAS -variant, no cetuximab and p16 negative, 0.61; 95% CI, 0.23-1.59; P = .02). Patients with the KRAS -variant had significantly elevated TGF-β1 plasma levels (median, 23 376.49 vs 18 476.52 pg/mL; P = .03) and worse treatment-related toxic effects. Conclusions and Relevance Patients with the KRAS- variant with HNSCC significantly benefit from the addition of cetuximab to radiotherapy and cisplatin, and there is a significant interaction between the KRAS -variant and p16 status. Elevated TGF-β1 levels in patients with the KRAS -variant suggests that cetuximab may help these patients by overcoming TGF-β1–induced suppression of antitumor immunity. Trial Registration clinicaltrials.gov Identifier:NCT00265941

212 Background: We present the first data evaluating overall treatment priorities, priorities specific to de-escalated therapy, treatment regret, and original expectations versus actual experiences among patients treated with de-escalated chemoradiation for human papillomavirus (HPV)-positive head and neck cancer (HNSCC). Methods: Participants were treated on a prospective phase II trial of induction chemotherapy followed by attenuated chemoradiotherapy for HPV-positive HNSCC. Eligible patients presented with stage III or IV squamous cell carcinoma of the oropharynx, p16-positivity, age ≥ 18 years, and Zubrod score 0-1. A total tumor dose of 60 Gy or 54 Gy was delivered depending on the response to induction chemotherapy. Participants were surveyed with validated measures evaluating their treatment experience. Results: Twenty-four out of 26 (92%) study patients participated with a median post-treatment follow-up of 20 months. 96% (n = 23) of participants selected ‘being cured’ or ‘living as long as possible’ to be their top priority. The highest-ranked priority with respect to treatment de-escalation was ‘to be able to swallow all foods and drinks’. No patient professed to any regret about the decision to enroll and be treated on a de-escalation protocol. 67% (n = 16) of participants reported long-term swallowing function to be either better than or as originally expected. 71% (n = 17) found long-term salivary function to be worse than expected. Overall, 63% (n = 15) of respondents found the severity of short-term side effects to be greater than expected, however, 63% (n = 15) of respondents found overall long-term toxicities to be less than originally expected. Conclusions: Among HPV-positive patients with HNSCC who had completed de-escalated therapy on a phase II protocol, cancer cure was the top overall priority, and preserving swallowing function was the highest priority for de-escalated therapy. No patient endorsed treatment regret, and the majority of patients found long-term swallowing outcomes to be better than or as originally expected. These data support ongoing studies aiming to establish the role of de-escalated therapies for HPV-positive HNSCC.

ObjectiveTo demonstrate the feasibility of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for the treatment of synchronous primary cancers arising from the head and neck.Methods14 consecutive patients with histologically proven squamous cell carcinoma of the head and neck were determined to have a second primary cancer in the upper aerodigestive tract on further evaluation and were treated with HT using simultaneous integrated boost IMRT. Megavoltage CT scans were acquired daily as part of an image-guided registration protocol. Concurrent platinum-based systemic therapy was given to nine patients (64%).ResultsHT resulted in durable local control in 21 of the 28 primary disease sites irradiated, including a complete clinical and radiographic response initially observed at 17 of the 20 sites with gross tumour. The mean displacements to account for interfraction motion were 2.44 ± 1.25, 2.92 ± 1.09 and 2.31 ± 1.70 mm for the medial-lateral (ML), superior-inferior (SI) and anteroposterior (AP) directions, respectively. Table shifts of >3 mm occurred in 19%, 20% and 22% of the ML, SI and AP directions, respectively. The 2-year estimates of overall survival, local-regional control and progression-free survival were 58%, 73% and 60%, respectively.ConclusionThe effectiveness of HT for the treatment of synchronous primary cancers of the head and neck was demonstrated.Advances in knowledgeHT is a feasible option for synchronous primary cancers of the head and neck and can result in long-term disease control with acceptable toxicity in appropriately selected patients.

PurposeUncertainty exists regarding the optimal surveillance imaging strategy following stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC), particularly with respect to timing. We sought to determine how routine use of early (

Purpose To evaluate the potential benefit of 4π radiation therapy in recurrent, locally advanced, or metastatic head-and-neck cancer treated with stereotactic body radiation therapy (SBRT). Methods and Materials Twenty-seven patients with 29 tumors who were treated using SBRT were included. In recurrent disease (n=26), SBRT was delivered with a median 44 Gy (range, 35-44 Gy) in 5 fractions. Three patients with sinonasal mucosal melanoma, metastatic breast cancer, and primary undifferentiated carcinoma received 35 Gy, 22.5 Gy, and 40 Gy in 5 fractions, respectively. Novel 4π treatment plans were created for each patient to meet the objective that 95% of the planning target volume was covered by 100% of the prescription dose. Doses to organs at risk (OARs) and 50% dose spillage volumes were compared against the delivered clinical SBRT plans. Local control (LC), late toxicity, tumor control probability (TCP), and normal tissue complication probability were determined. Results Using 4π plans, mean/maximum doses to all OARs were reduced by 22% to 89%/10% to 86%. With 4π plans, the 50% dose spillage volume was decreased by 33%. Planning target volume prescription dose escalation by 10 Gy and 20 Gy were achieved while keeping doses to OARs significantly improved or unchanged from clinical plans, except for the carotid artery maximum dose at 20-Gy escalation. At a median follow-up of 10 months (range, 1-41 months), crude LC was 52%. The 2-year LC of 39.2% approximated the predicted mean TCP of 42.2%, which increased to 45.9% with 4π plans. For 10-Gy and 20-Gy dose escalation, 4π plans increased TCP from 80.1% and 88.1% to 85.5% and 91.4%, respectively. The 7.4% rate of grade ≥3 late toxicity was comparable to the predicted 5.6% mean normal tissue complication probability for OARs, which was significantly reduced by 4π planning at the prescribed and escalated doses. Conclusions 4π plans may allow dose escalation with significant and consistent improvements in critical organ sparing, tumor control, and coverage.

ObjectiveTo evaluate the dose received by the hippocampus among patients undergoing intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer.Methods10 patients with biopsy-proven, locally advanced nasopharyngeal cancer constituted the study population. The total prescribed dose to the planning target volume (PTV) was 70 Gy (D95%) delivered in 2.12-Gy daily fractions using IMRT. Using established anatomical guidelines, MRI co-registration and the assistance of a board-certified neuroradiologist, the right and left hippocampi were delineated on axial imaging from the CT scan obtained at simulation for each patient beginning at the most anterior portion of the lateral ventricle. IMRT treatment plans were generated without dose-volume constraints to the hippocampus. A range of dose-volume statistics was calculated.ResultsThe mean hippocampus volume was 6.01 ± 2.61 cm(3). The mean V20 was 72.2%; V40 was 22.0%; V50 was 10.2%; and V60 was 5.5%. The average mean, minimum and maximum hippocampus doses were 30.27 Gy (range, 19.08-47.99 Gy); 17.54 Gy (range, 11.66-33.17 Gy); and 54.95 Gy (range, 35.59-75.57 Gy), respectively. The hippocampus received a maximum dose exceeding 70 Gy in 30% of cases.ConclusionOur dosimetric analysis suggests that, for patients undergoing IMRT for nasopharyngeal cancer, the hippocampus routinely receives significantly high doses.Advances in knowledgeThe hippocampus receives a fair amount of incidental radiation during treatment for nasopharyngeal cancer. Given the importance of this structure with respect to memory and neurocognitive function, consideration should be given to identifying the hippocampus as a critical organ at risk in the IMRT optimization process.

Submandibular gland-sparing intensity-modulated radiotherapy (SMG-sparing IMRT) has been proposed to reduce xerostomia following head and neck irradiation. However, the safety of this practice has been questioned. Data from a large surgical series of oropharyngeal carcinoma patients were extracted to identify clinicopathological correlates for submandibular involvement and to create a risk stratification scheme to guide decision making to refine selection guidelines for SMG-sparing IMRT.Clinicopathologic analysis.The medical records of 153 consecutive patients with squamous cell carcinoma of the oropharynx treated by primary surgery and neck dissection were reviewed. Univariate and multivariate analysis was performed with logistic regression to identify factors predictive of submandibular involvement. Recursive partitioning was used to develop risk stratification schemas based on preoperative data alone and in combination with pathologic data to guide treatment decisions in the definitive and postoperative settings, respectively.Submandibular (level IB) nodal dissection was performed in 119 heminecks (85 ipsilateral and 17 contralateral). The incidence of submandibular involvement was 18%. Young age, T3-4 disease, N2b-3 disease, and perineural invasion were identified as risk factors for submandibular nodal involvement on multivariate analysis (P .01). Three distinct risk groups for submandibular involvement were identified: age60 years and N0-2a disease (low risk, 2%), age ≤60 years and T1-2N2b-3 (intermediate risk, 16%), age ≤60 years and T3-4N2b-3 disease (high risk, 57%).These data provide assurances that SMG-sparing IMRT can reasonably be offered to appropriately selected patients. Risk stratification schemas were successfully developed for SMG-sparing IMRT in both the definitive and adjuvant settings.

To quantify changes in gross tumour volume (GTV) between simulation and initiation of radiotherapy in patients with locally advanced malignancies of the lung and head/neck.Initial cone beam computed tomography (CT) scans from 12 patients with lung cancer and 12 with head/neck cancer (head and neck squamous cell carcinoma (HNSCC)) treated with intensity-modulated radiotherapy with image guidance were rigidly registered to the simulation CT scans. The GTV was demarcated on both scans. The relationship between percent GTV change and variables including time interval between simulation and start, tumour (T) stage, and absolute weight change was assessed.For lung cancer patients, the GTV increased a median of 35.06% (range, -16.63% to 229.97%) over a median interval of 13 days (range, 7-43), while for HNSCC patients, the median GTV increase was 16.04% (range, -8.03% to 47.41%) over 13 days (range, 7-40). These observed changes are statistically significant. The magnitude of this change was inversely associated with the size of the tumour on the simulation scan for lung cancer patients (P 0.05). However, the observed changes in GTV did not correlate with the duration of the interval for either disease site. Similarly, T stage, absolute weight change and histologic type (the latter for lung cancer cases) did not correlate with degree of GTV change (P 0.1).While the observed changes in GTV were moderate from the time of simulation to start of radiotherapy, these findings underscore the importance of image guidance for target localisation and verification, particularly for smaller tumours. Minimising the delay between simulation and treatment initiation may also be beneficial.

Background The purpose of this study was to analyze the pattern of occult cervical lymph node metastasis among patients with clinically N0 salivary gland carcinoma. Methods One hundred nineteen patients underwent primary surgery and ipsilateral neck dissection for clinically N0 carcinomas of the major and minor salivary glands. Eighty patients (67%) had parotid tumors. Distribution of T classification was: T1 (18%), T2 (28%), T3 (23%), and T4 (32%). Results Twenty-five patients (21%) had pathological cervical disease. The incidence was highest among patients with adenocarcinoma (35%) and high-grade mucoepidermoid carcinoma (35%). The most common site of cervical lymph node metastasis was level II (71%), followed by level III (15%), and level IB (8%). On multivariate analysis, histological subtype was independently predictive of occult pathological lymph node metastasis (p < .001). Conclusion The likelihood of occult cervical lymph node metastasis for patients with salivary gland carcinoma is driven predominantly by histological subtype. Implications for elective neck irradiation are discussed. © 2014 Wiley Periodicals, Inc. Head Neck, 36: 1435–1439, 2014

ObjectiveTo characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours.Methods40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V10, V20 and V30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC).ResultsThe maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V10, V20 and V30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V20 was identified as the most significant predictor of late toxicity (AIC, 26.81).ConclusionA dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future.Advances in knowledgeA threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.

Patients with stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) do not undergo a staging mediastinoscopy, yet reported mediastinal recurrence rates appear lower than in patients undergoing surgical resection. We determined incidental SBRT doses to assess whether this could account for the low rates of recurrence.Between March 2009 and September 2012, we reviewed cases of patients with inoperable lung tumors (n = 136) treated with SBRT at our institution. The SBRT regimen was 54 Gy in 3 fractions with positron emission tomography/computed tomography (PET/CT) staging. Incidental doses to the mediastinal lymph node stations (MLNSs), primary tumor control, locoregional (LR), distant control (DC), and overall survival (OS) rates were determined.Forty-six patients with stage I NSCLC met the inclusion criteria. The calculated median incidental SBRT dose to all MLNSs was5 Gy for the majority of patients (75%). At a median follow-up of 16.8 months (0.6-38.9 months), the 1- and 2-year primary tumor control, LR, OS, and DC rates were 100% and 95.5%, 97.4% and 81.7%, 88.1% and 81%, and 96.9% and 86.9%, respectively. Only 2 patients (4.9%) had mediastinal recurrence, with incidental SBRT doses to MLNSs that were similar to the rest of patients (P.05).Low mediastinal recurrence rates in stage I NSCLC treated with SBRT validates the omission of staging mediastinoscopy. The low incidental dose to MLNSs does not seem to explain the low mediastinal recurrence in the majority of patients. Our findings also confirm that prophylactic radiation to the mediastinum is not necessary and support the hypothesis that local ablation of the primary lesion could indirectly affect subclinical nodal disease through unknown mechanisms.

The purpose of this study was to compare outcomes among patients treated by intensity-modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT) for head and neck cancer according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV).Three hundred sixty-seven consecutive patients were treated with IMRT for squamous cell carcinoma of the head and neck. The first 103 patients were treated with 5-mm CTV-to-PTV margins. The subsequent 264 patients were treated using reduced (3 mm) margins.The 3-year locoregional control for patients treated using 5-mm and 3-mm CTV-to-PTV margins, respectively, was 78% and 80% (p = .75). The incidence of gastrostomy-tube dependence at 1 year was 10% and 3%, respectively (p = .001). The incidence of posttreatment esophageal stricture was 14% and 7%, respectively (p = .01).The use of reduced (3 mm) CTV-to-PTV margins was associated with reduced late toxicity while maintaining locoregional control.

A calibration curve for chronic exposure to 137 Cs gamma rays is required for biological dosimetry of individuals exposed in connection with Chernobyl and other radiation accidents involving radiocaesium. Here, chromosome painting was used to measure the frequencies of reciprocal translocations in human lymphocytes following protracted exposures in vitro to 0.29, 0.62, and 0.95 Gy of 137 Cs gamma rays. The exposures were delivered continuously during 48 h. A reliable measure of the linear slope (α coefficient) of the dose-response curve was obtained by analysing 18,389 metaphase lymphocytes in the irradiated samples and 25,067 in the controls. The α coefficient was measured to be 0.030 ± 0.003 translocation per cell per Gy when fitting the data with a linear model using a weighted least square method and a very similar 0.029 ± 0.009 translocation per cell per Gy when fitted with a weighted least square: linear-quadratic model. These results provide a calibration curve for biodosimetry involving protracted or low dose exposures to 137 Cs gamma rays, where the α coefficient defines the induced translocation frequency.

We used three common fluorescent probes to measure pericentric inversion frequencies in 2.9 Gy 60Co gamma-irradiated human lymphocytes. For a given chromosome, the first probe is specific to one telomeric region, the second probe is specific to one subcentromeric region and the third probe is specific to the centromere. A pericentric inversion is made observable by the change in position (switching) of the fluorescent signals relative to the chromosome centromere. Our data showed equality between pericentric inversions and centric rings. The calculated whole-genome F-ratio of apparently simple translocations to pericentric inversions was 5.6.

After ionizing radiation has induced double-strand DNA breaks (dsb), misrejoining produces chromosome aberrations. Aberration yields are influenced by "proximity' effects, i.e., by the dependence of misrejoining probabilities on initial dsb separations. We survey proximity effects, emphasizing implications for chromosome aberration-formation mechanisms, for chromatin geometry, and for dose-response relations. Evidence for proximity effects comes from observed biases for centric rings and against three-way interchanges, relative to dicentrics or translocations. Other evidence comes from the way aberration yields depend on radiation dose and quality, tightly bunched ionizations being relatively effective. We concludes (1) that misrejoining probabilities decrease as the distance between dsb at the time of their formation increases, and almost all misrejoining occurs among dsb initially separated by < 1/3 of a cell nucleus diameter; (2) that chromosomes occupy (irregular) territories during the G0/G1 phase of the cell cycle, having dimensions also roughly 1/3 of a cell nucleus diameter, (3) that proximity effects have the potential to probe how much different chromosomes intertwine on move relative to each other: and (4) that incorporation of proximity effects into the classic random breakage-and-reunion model allows quantitative interrelation of yields for many different aberration types and of data obtained with various FISH painting methods or whole-genome scoring.

The purpose of this study was to compare patient-reported outcomes between patients treated by initial transoral resection versus definitive chemoradiotherapy for oropharyngeal cancer.Thirty-one patients with oropharyngeal cancer treated by initial transoral CO2 laser microsurgery (n = 16) or robotic surgery (n = 15) followed by postoperative radiotherapy were identified. Each patient was matched to 1 control patient treated by definitive chemoradiotherapy. The University of Washington Quality of Life (UW-QOL) scores at 1 year were compared.No significant differences were observed in any of the UW-QOL functional domains at 1 year with the exception of swallowing (91.5 vs 72.1; p = .01). Twenty-three of 31 patients (74%) treated by transoral surgery reported swallowing "as well as ever," versus 10 of 31 patients (32%) treated by chemoradiotherapy.Similar quality of life was observed among patients treated by transoral surgery or chemoradiotherapy. Although the rates of subjective swallowing dysfunction were higher among the latter, confounding biases must be considered.

With an annual incidence of less than 1 per million, salivary gland malignancies in children are rare, constituting less than 10% of pediatric head and neck cancer. Although over 20 histologic types of salivary gland cancer have been reported in adults, a smaller number have been observed in the pediatric population. Mucoepidermoid carcinoma is the most common histologic type, followed by acinic cell carcinoma. Since the majority of salivary gland carcinomas are diagnosed at an early stage, the overall prognosis is often favorable with complete surgical resection. To date, no prospective or retrospective data comparing outcomes of surgery alone versus multimodality therapy in the management of salivary gland malignancies in the pediatric population exists. Consequently, management decisions are made on a case-by-base basis, taking prognosis, treatment-related morbidity, and long-term sequelae into account.

This paper aimed to systematically review the (1) prevalence, (2) risk factors, (3) interventions, and (4) measurement instruments associated with psychosocial function decline in radiation therapy (RT) patients.A MEDLINE systematic literature review was performed to identify studies monitoring psychosocial function among RT patients as a primary endpoint.Fifty-seven and 22 risk factors for RT-related psychosocial function decline were identified and refuted, respectively, in 93 eligible studies representing 12,808 patients. Median prevalences of psychosocial function decline prior to, during, and following RT were 20%, 36%, and 25%. Prior to RT, anxiety was more prevalent than depression (20% vs 15%), but dropped following completion of RT, whereas median depression levels remained elevated (17% vs. 27%). Of the 79 identified risk factors, 17 were reported as predictive of psychosocial decline by two or more more studies, and five had robust support: (1) physical symptoms, (2) time point during RT, (3) chemotherapy reception, (4) female gender, and (5) younger age. Three interventions were consensually reported to improve psychosocial function: psychotherapy, nursing consultation/patient education, and self-management training. Eighty-six different assessment tools were used to monitor RT-related psychosocial function decline with the Hospital Anxiety and Depression Scale (25.8%) and the psychiatric interview (22.6%) being the most utilized. The distress thermometer has been used in 5 studies (5.4%) to date.Psychosocial function declines in approximately one-third of RT patients. Anxiety can dissipate after initiation of RT, whereas depression can persist throughout and after RT. Severe physical symptoms and time-related factors most robustly predict psychosocial function decline, which can be improved by psychotherapy and interventions aimed to improve patient education.

To analyze outcomes among patients with residual positron-emission tomography (PET)-negative lymphadenopathy after chemoradiotherapy for head and neck cancer based on whether or not they underwent neck dissection.Retrospective review.Fifty-five patients with stage III/IV squamous cell carcinoma of the head and neck were identified with residual PET-negative lymphadenopathy based on standardized uptake value of3. All patients had been treated with chemoradiotherapy to a median dose of 70 Gy (range, 60-4 Gy).With a median follow-up of 30 months (range, 6-67 months), the 3-year overall survival (85% vs. 81%, P = .57), progression-free survival (88% vs. 88%, P = .42), and local-regional control (96% vs. 100%, P = .68), did not differ between patients treated by neck dissection or observation.Omission of neck dissection appears to be reasonable for patients with residual lymphadenopathy but negative PET after chemoradiotherapy for head and neck cancer.4.

Objectives/Hypothesis To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Study Design Retrospective review. Methods The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. Results The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). Conclusion Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future. Level of Evidence 4. Laryngoscope, 123:3049–3055, 2013

Introduction The benefit of local therapy in the form of surgery or radiation therapy to the chest wall or intact breast remains unproven in patients diagnosed with stage IV breast cancer. Traditional therapy for these patients consisted of primary systemic therapy, with surgery or radiation therapy reserved for palliation of symptomatic local disease only after control of systemic disease. Stage IV breast cancer patients constitute a heterogeneous population with regard to molecular subtype, age, overall disease burden, visceral organ involvement, and treatment response to endocrine therapy, biologic agents, or chemotherapy, all of which contribute to prognosis. With the advent of new therapeutic strategies, the 3-year survival rate increased from 27% to 44% in a French multicenter study. With the increasing efficacy of systemic therapy, a subgroup of stage IV patients may achieve a complete clinical and radiologic response. Emerging data, mostly examining the efficacy of surgery, suggest an overall survival (OS) advantage with aggressive management of the primary site of disease in stage IV breast cancer. Similar findings to support surgical resection in select stage IV patients have also been reproduced with the database of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and institutional observational protocols. The benefit of radiation therapy to the primary tumor, either following or replacing surgery, in this cohort of patients remains unknown. Our clinical commentary visits the role of locoregional therapy of the primary tumor in patients with metastatic disease at diagnosis. Further, we explore the existing data and the potential role of radiation in this setting.

Objectives/Hypothesis To examine functional and quality-of-life outcomes for patients treated by reirradiation to the head and neck for recurrent or new primary cancers. Study Design Retrospective review. Methods The University of Washington Quality of Life Instrument (UW-QOL) scores were reviewed with swallow evaluations for 17 patients with biopsy-proven recurrent or new primary squamous cell carcinoma of the head and neck treated with reirradiation who were clinically without evidence of disease at a minimum follow-up of 1 year. All patients had received their initial radiation therapy to a median dose of 66 Gy (range, 60–72 Gy). The median interval between radiation courses was 30 months (range, 6–132 months). The median reirradiation dose was 60 Gy (range, 54–70 Gy). Results At 1 year after reirradiation, the mean UW-QOL composite score was 67.0 (range, 22.1–83.5), which did not differ significantly from baseline (P = .57). The proportion of patients who rated their global quality of life as “very good” or “outstanding” at 1 year after reirradiation was 35%. The percentage of patients who reported their global quality of life as “good/fair” and “poor/very poor” were 59% and 6%, respectively. Conclusions The majority of survivors in this highly selected series were devoid of new impairment after reirradiation and were satisfied with their functional status. Although nearly all patients had side effects from their prior radiation course prior to reirradiation, no patient reported a decline in global quality of life from before reirradiation to 1 year post-treatment. Level of Evidence 2c Laryngoscope, 124:1807–1812, 2014

The purpose of this study was to analyze the pattern of occult cervical lymph node metastasis among patients with clinically N0 salivary gland carcinoma.One hundred nineteen patients underwent primary surgery and ipsilateral neck dissection for clinically N0 carcinomas of the major and minor salivary glands. Eighty patients (67%) had parotid tumors. Distribution of T classification was: T1 (18%), T2 (28%), T3 (23%), and T4 (32%).Twenty-five patients (21%) had pathological cervical disease. The incidence was highest among patients with adenocarcinoma (35%) and high-grade mucoepidermoid carcinoma (35%). The most common site of cervical lymph node metastasis was level II (71%), followed by level III (15%), and level IB (8%). On multivariate analysis, histological subtype was independently predictive of occult pathological lymph node metastasis (p.001).The likelihood of occult cervical lymph node metastasis for patients with salivary gland carcinoma is driven predominantly by histological subtype. Implications for elective neck irradiation are discussed.

The purpose of this study was to determine the effect of adaptive replanning on clinical outcome among patients treated by intensity-modulated radiotherapy (IMRT) for head and neck cancer.Three hundred seventeen patients underwent IMRT with daily image-guidance for newly diagnosed squamous cell carcinoma of the head and neck to a median dose of 66 Gy (range, 60-74 Gy). Of these 317 patients, 51 (16%) underwent adaptive radiotherapy with modification of the original IMRT midway during treatment.The 2-year local-regional control was 88% for patients treated with adaptive replanning compared with 79% for patients treated without (p = .01). The median time to local-regional recurrence for the 4 patients treated by adaptive radiotherapy was 7 months (range, 3-15 months) with all failures occurring within the high-dose planning target volume (PTV).Although the use of routine replanning is probably not necessary, our findings do suggest a significant benefit in appropriately selected patients.

A Monte Carlo simulation computer program for radiation-produced chromosome aberrations, based on the breakage-and-reunion model, was extended to include proximity effects due to localization of chromosomes and limited range for break-break interactions. Two adjustable parameters were used. One corresponds to total dose: the other determines proximity effects by specifying the number of 'interaction regions' in a cell nucleus. The use of additional adjustable parameters was avoided by assuming randomness of break induction and aberration production. FISH chromosome painting data were obtained from 1.9 Gy 60Co gamma-rays-irradiated human lymphocytes. The data were compared with the computer simulation results, taking individual chromosome lengths into account. With about 13 interaction regions, agreement between the experiment and the simulation was good, even when detailed categories of damage were scored. An estimated average dsb-dsb interaction distance, based on 13 interaction regions, is about 1.3 micron. Monte Carlo methods give useful quantitative estimates of relative aberration yields, with a minimum of adjustable parameters and the theoretical assumptions, and indicated proximity effects. Computer simulation of FISH experiments can be adapted to any number of colours, any scoring criteria and any method of grouping aberrations into categories. Simulation allows systematic extrapolation of aberration data on painted chromosomes to whole-genome aberration frequencies.