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Objectives: To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. Methods: We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. Results: DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictormuscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Conclusions: Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx. [ABSTRACT FROM AUTHOR]

BACKGROUND: Psychosocial interventions often address only 1 domain of quality of life (QOL), are offered to patients with early-stage cancer, do not include the caregiver, and are delivered after cancer treatment has been completed. METHODS: In the current randomized controlled trial, 131 patients with advanced cancer who received radiotherapy and their caregivers were randomly assigned to either a 6-session, structured, multidisciplinary intervention arm or a standard care arm. The average age of the patients was 58 years, the majority were male (63%), and tumor types varied (gastrointestinal [37%], brain [22%], head and neck [16%], lung [13%], and other [12%]). The six 90-minute sessions addressed the 5 domains of QOL: cognitive, physical, emotional, social, and spiritual. The in-person intervention was followed by 10 brief telephone counseling sessions that took place over the next 6 months. RESULTS: Of the 117 patients who completed the study, overall QOL (assessed by Functional Assessment of Cancer Therapy-General [FACT-G]) at week 4 was significantly higher in the intervention group (n = 54) compared with the standard arm control group (n = 63) (75.2 vs 68.7; P = .02). The 10 brief telephone contacts did not appear to impact QOL because at week 27 the groups had identical QOL (means of 77.6 and 77.7, respectively). There was no effect of the intervention noted on caregiver QOL. CONCLUSIONS: Participating in a 6-session multidisciplinary intervention was found to be effective in maintaining the QOL of patients with advanced cancer who were actively receiving radiotherapy. The QOL and symptom burden of this population is striking, making it important to identify effective QOL strategies to implement in conjunction with cancer care. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose: To study the long-term survival of dental implants placed in irradiated bone in subjects who received radiation for head and neck cancer. Materials and Method: A retrospective chart review was conducted for all patients who received dental implants following radiation treatment for head and neck cancer between May 1, 1987 through July 1, 2008. Only patients irradiated with a radiation dose of 50 Gy or greater and those who received dental implants in the irradiated field after head and neck radiation were included in the study. The associations between implant survival and patient/implant characteristics were estimated by fitting univariate marginal Cox proportional hazards models. Results: A total of 48 patients who had prior head and neck radiation had 271 dental implants placed during May 1987 to July 2008. The estimated survival at 1, 5, and 10 years was 98.9%, 89.9%, and 72.3%, respectively. Implants placed in the maxilla were more likely to fail than implants placed in the mandible ( p = .002).There was also a tendency for implants placed in the posterior region to fail compared with those placed in the anterior region ( p = .051). Conclusion: Dental implants placed in irradiated bone have a greater risk for failure. Survival is significantly influenced by the location of the implant (maxilla or mandible, anterior or posterior). [ABSTRACT FROM AUTHOR]

Abstract: Combined modality therapy is the standard care for limited stage-small cell lung cancer (LS-SCLC) and has led to a significant improvement in patients’ survival. This study sought to investigate and define the importance of prognostic effects of known and controversial factors especially the impact of smoking status and treatment strategies. A total of 284 patients with LS-SCLC were diagnosed and prospectively followed from 1997 to 2008 at Mayo Clinic; their characteristics and survival outcome were assessed on the basis of age, gender, smoking history, performance status (PS), tumor recurrence or progression, and treatment using Cox proportional hazards models. Our main results are as follows: (1) Although neither smoking status (former or current smokers) nor intensity (pack-years smoked) at the time of SCLC diagnosis were significant survival predictors, compared to continued smokers (who never quit smoking), patients who quit at or after diagnosis cut the risk of death by 45% (HR=0.55, 95% CI 0.38–0.79); patients who quit before lung cancer diagnosis also experienced survival benefit (HR=0.72, 95% CI 0.52–1.00). (2) Thoracic radiotherapy and platinum-based chemotherapy could significantly improve survival but the timing (within or after one month of diagnosis) of starting chemotherapy or radiation therapy did not. (3) After adjusting for other known factors, a lower PS did not predict poorer survival, suggesting that PS should not be the only factor for making treatment decisions. In conclusion, this study demonstrated the negative impact of continued cigarette smoking on survival; therefore, clinicians and all care providers should strongly encourage smoking cessation at diagnosis of LS-SCLC. [Copyright &y& Elsevier]

: PurposeTo determine the role that radiation therapy may have in the management of resected, unresectable, and metastatic Hu¨rthle cell carcinoma.: Methods and materialsRetrospective review of 18 patients receiving radiation therapy for Hu¨rthle cell carcinoma of the thyroid gland. The diagnosis was established in 10 men and 8 women between November 1943 and January 1995. Median age was 57.9 years. Initially, 5 patients received adjuvant radiation therapy, 7 received salvage radiation therapy for unresectable recurrent disease, and 6 received palliative radiation therapy for distant metastases. Median follow-up was 107.1 months (range 15.7–351 months). The Kaplan-Meier method was used to calculate and estimate overall survival, cause-specific survival, and locoregional tumor control rate.: ResultsThe 5-year overall and cause-specific survival rates were 66.7% (SE 11.1%) and 71.8% (SE 10.7%), respectively. Adjuvant radiation therapy was successful in preventing recurrence in 4 of 5 patients. Salvage radiation therapy was successful in 3 of 5 patients treated with external beam radiation therapy. Palliative radiation therapy provided sustained symptomatic relief at 67% of irradiated sites.: ConclusionsHu¨rthle cell carcinoma of the thyroid gland is a radiosensitive tumor. Radiation therapy may provide palliative relief from symptomatic metastases, control recurrent tumors, and prevent recurrence of advanced resected tumors. [Copyright &y& Elsevier]

Purpose: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS).Methods and Materials: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 years (range, 5-24.9 years).Results: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation.Conclusions: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS for appropriate patients. [ABSTRACT FROM AUTHOR]

Summary Background We aimed to compare overall survival after standard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer. Methods In this open-label randomised, two-by-two factorial phase 3 study in 185 institutions in the USA and Canada, we enrolled patients (aged ≥18 years) with unresectable stage III non-small-cell lung cancer, a Zubrod performance status of 0–1, adequate pulmonary function, and no evidence of supraclavicular or contralateral hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All patients also received concurrent chemotherapy with 45 mg/m 2 paclitaxel and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel (200 mg/m 2 ) and carboplatin (AUC 6). Randomisation was done with permuted block randomisation methods, stratified by radiotherapy technique, Zubrod performance status, use of PET during staging, and histology; treatment group assignments were not masked. Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy. The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary. For patients assigned to receive cetuximab, 400 mg/m 2 cetuximab was given on day 1 followed by weekly doses of 250 mg/m 2 , and was continued through consolidation therapy. The primary endpoint was overall survival. All analyses were done by modified intention-to-treat. The study is registered with ClinicalTrials.gov , number NCT00533949 . Findings Between Nov 27, 2007, and Nov 22, 2011, 166 patients were randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up for the radiotherapy comparison was 22·9 months (IQR 27·5–33·3). Median overall survival was 28·7 months (95% CI 24·1–36·9) for patients who received standard-dose radiotherapy and 20·3 months (17·7–25·0) for those who received high-dose radiotherapy (hazard ratio [HR] 1·38, 95% CI 1·09–1·76; p=0·004). Median follow-up for the cetuximab comparison was 21·3 months (IQR 23·5–29·8). Median overall survival in patients who received cetuximab was 25·0 months (95% CI 20·2–30·5) compared with 24·0 months (19·8–28·6) in those who did not (HR 1·07, 95% CI 0·84–1·35; p=0·29). Both the radiation-dose and cetuximab results crossed protocol-specified futility boundaries. We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups. By contrast, the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects (205 [86%] of 237 vs 160 [70%] of 228 patients; p<0·0001). There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups (radiotherapy comparison: eight vs three patients; cetuximab comparison: ten vs five patients). There were no differences in severe pulmonary events between treatment groups. Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received standard-dose treatment (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p<0·0001). Interpretation 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung can [ABSTRACT FROM AUTHOR]

Background: This prospective cohort study was designed to determine whether the amount of radiation delivered to the nonpathological lymph nodes (LNs) that drain the arm can be significantly reduced by integrating single-photon emission computed tomography (SPECT)/computed tomography (CT) scans into radiation treatment planning. Methods: SPECT-CT scans were acquired for the 28 patients with stage I or II breast cancer and fused with the routinely obtained radiation oncology planning CT scans. Arm-draining LNs were contoured with 0.5-cm margins automatically using a threshold of 50% maximum intensity. Two treatment plans were generated: 1 per routine clinical practice (standard; STD) and the second (modified; MOD) with treatment fields modified to minimize dose to the arm-draining LNs visible on SPECT/CT images without interfering with the dosage delivered to target tissues. Participants were treated per the MOD plans. Arm volumes were measured prior to radiation and thereafter at least three subsequent 6-month intervals. Results: Sixty-eight level I-III arm-draining LNs were identified, 57% of which were inside the STD plan fields but could be blocked in the MOD plan fields. Sixty-five percent of arm-draining LNs in the STD versus 16% in the MOD plans received a mean of ≥10 Gy, and 26% in the STD versus 4% in the MOD plans received a mean of ≥40 Gy. Mean LN radiation exposure was 23.6 Gy (standard deviation 18.2) with the STD and 7.7 Gy (standard deviation 11.3) with the MOD plans (P<.001). No participant developed lymphedema. Conclusions: The integration of SPECT/CT scans into breast cancer radiation treatment planning reduces unnecessary arm-draining LN radiation exposure and may lessen the risk of lymphedema. [Copyright &y& Elsevier]

Purpose: To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected patients with limited-disease small-cell lung cancer (LD SCLC). Methods and Materials: Patients with LD SCLC who achieved a complete response after chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 fractions (Arm 2) and twice-daily 24 fractions (Arm 3). Enrolled patients participated in baseline and follow-up neuropsychological test batteries along with quality-of-life assessments. Results: A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2, and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3 months of median follow-up. There were no significant baseline differences among groups regarding quality-of-life measures and one of the neuropsychological tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI there was a significant increase in the occurrence of CNt in the 36-Gy cohort (p = 0.02). Logistic regression analysis revealed increasing age to be the most significant predictor of CNt (p = 0.005). Conclusions: Because of the increased risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy remains the standard of care for patients with LD SCLC attaining a complete response to initial chemoradiation. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. Material and methods: A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. Results: With a median follow-up of 15.8months (range 2.5–28.6), the median age at SBRT was 71.8years (range 23.8–87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ⩾2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. Conclusions: Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity. [Copyright &y& Elsevier]

Purpose: Proton radiotherapy (PT) and stereotactic body radiotherapy (SBRT) have the capacity to optimize the therapeutic ratio. We analyzed the dosimetric differences between PT and SBRT in treating primary peripheral early-stage non–small-cell lung cancer. Methods and Materials: Eight patients were simulated, planned, and treated with SBRT according to accepted techniques. SBRT treatments were retrospectively planned using heterogeneity corrections. PT treatment plans were generated using single-, two-, and three-field passively scattered and actively scanned proton beams. Calculated dose characteristics were compared. Results: Comparable planning target volume (PTV) median minimum and maximum doses were observed between PT and SBRT plans. Higher median maximum doses 2 cm from the PTV were observed for PT, but higher median PTV doses were observed for SBRT. The total lung mean and V5 doses were significantly lower with actively scanned PT. The lung V13 and V20 were comparable. The dose to normal tissues was lower with PT except to skin and ribs. Although the maximum doses to skin and ribs were similar or higher with PT, the median doses to these structures were higher with SBRT. Passively scattered plans, compared with actively scanned plans, typically demonstrated higher doses to the PTV, lung, and organs at risk. Conclusions: Single-, two-, or three-field passively or actively scanned proton therapy delivered comparable PTV dose with generally less dose to normal tissues in these hypothetic treatments. Actively scanned beam plans typically had more favorable dose characteristics to the target, lung, and other soft tissues compared with the passively scanned plans. The clinical significance of these findings remains to be determined. [Copyright &y& Elsevier]