GammaKnife versus VMAT radiosurgery plan quality for many brain metastases.

The purpose of this work was to compare dose distributions between two radiosurgery modalities, single-isocenter volumetric modulated arc therapy (VMAT), and GammaKnife Perfexion (GK), in the treatment of a large number (≥7) of brain metastases. Twelve patients with 103 brain metastases were analyzed. The median number of targets per patient was 8 (range: 7-14). GK plans were compared to noncoplanar VMAT plans using both 6-MV flattening filter-free (FFF) and 10-MV FFF modes. Parameters analyzed included radiation therapy oncology group conformity index (CI), 12, 6, and 3 Gy isodose volumes (V12 Gy, V6 Gy, V3 Gy), mean and maximum hippocampal dose, and maximum skin dose. There were statistically significant differences in CI (2.5 ± 1.6 vs 1.6 ± 0.8 and 1.7 ± 0.9, P < 0.001, P < 0.001), V12 Gy (2.8 ± 6.1 cc vs 3.0 ± 5.2 cc and 3.1 ± 5.4 cc, P = 0.003, P < 0.001), and V3 Gy (323.0 ± 294.8 cc vs, 880.1 ± 369.1 cc and 937.9 ±  vs 361.9 cc, P = 0.005, P = 0.001) between GK versus both 6-MV FFF and 10-MV FFF. No significant differences existed for maximum hippocampal or skin doses. In conclusion, highly optimized VMAT produced improved conformity at the expense of a higher V12 Gy and V3 Gy volume when compared with highly optimized GK.

Implementation Readiness and Initial Effects of a Brief Mindfulness Audio Intervention Compared With a Brief Music Control During Daily Radiation Therapy for Prostate Cancer: A Randomized Pilot Study.

Background: The most common and debilitating side effects of radiation therapy (RT) for prostate cancer (PC) are fatigue, sleep disturbance, anxiety, and depression. Previous research has reported palliative benefits from certain self-management approaches, such as mindfulness meditation. Objective: To develop, pre-test, and evaluate the feasibility, acceptability and initial benefit of brief, audio-based mindfulness delivered during daily RT for PC compared to a relaxing music control. Methods: Following intervention development, participants were randomized to either brief guided mindfulness audio recordings or a relaxing music control during daily RT. A pre-testing phase was first conducted to determine optimal program start time, length, and content most associated with retention. A final program (n = 26) was delivered daily, starting on day one of week 2 of RT and lasting 4 consecutive weeks. Feasibility was defined as ≥70% on enrollment rate, retention, and audio program adherence. Acceptability was measured with a 12-item post-study survey. A secondary focus compared between group changes on patient reported outcomes of fatigue, anxiety, depression, sleep disturbance, and related outcomes at baseline and follow up assessments. Descriptive statistics and general linear models were used. Results: Overall, 76% (n = 38) of approached men enrolled. Pre-testing retention rates were <70% while the final program's retention rate was 89%. The majority of acceptability criteria were met in both conditions, with relatively higher ratings in the mindfulness arm. Compared to music controls, mindfulness participants demonstrated significantly less uncertainty intolerance at 4-weeks (P = .046, d = .95); and significantly lower fatigue scores (P = .049, d = 1.3) and lower sleep disturbance scores (P = .035, d = 1.1) at the 3 months follow up. Conclusion: The final intervention met feasibility and acceptability criteria. Pre-testing refinements played a key role for optimal program delivery and retention. Audio-based mindfulness delivered during RT for PC hold potential to help decrease RT-related physical and emotional side effects.

Early findings on toxicity of proton beam therapy with concurrent chemotherapy for nonsmall cell lung cancer.

BACKGROUND: Concurrent chemoradiation therapy, the standard of care for locally advanced nonsmall cell lung cancer (NSCLC), can cause life-threatening pneumonitis and esophagitis. X-ray (photon)-based radiation therapy (RT) often cannot be given at tumoricidal doses without toxicity to proximal normal tissues. We hypothesized that proton beam therapy for most patients with NSCLC could permit higher tumor doses with less normal-tissue toxicity than photon RT delivered as 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: We compared the toxicity of proton therapy+concurrent chemotherapy in 62 patients with NSCLC (treatment period 2006-2008) with toxicity for patients with similar disease given 3D-CRT+chemotherapy (n = 74; treatment period 2001-2003) or IMRT+chemotherapy (n = 66; treatment period 2003-2005). Proton therapy to the gross tumor volume was given with weekly intravenous paclitaxel (50 mg/m²) and carboplatin (area under the curve 2 mg/mL/min). The primary endpoint was toxicity (Common Terminology Criteria for Adverse Events version 3.0). RESULTS: Median follow-up times were 15.2 months (proton), 17.9 months (3D-CRT), and 17.4 months (IMRT). Median total radiation dose was 74 Gy(RBE) for the proton group versus 63 Gy for the other groups. Rates of severe (grade ≥ 3) pneumonitis and esophagitis in the proton group (2% and 5%) were lower despite the higher radiation dose (3D-CRT, 30% and 18%; IMRT, 9% and 44%; P<.001 for all). CONCLUSIONS: We found that higher doses of proton radiation could be delivered to lung tumors with a lower risk of esophagitis and pneumonitis. A randomized comparison of IMRT versus proton therapy is underway.

Comparison of three methods to increase knowledge about breast cancer and breast cancer screening in screening mammography patients.

RATIONALE AND OBJECTIVES: The specific aim of the study was to determine which of several cost-effective interventions is best able to improve the breast cancer knowledge of women who present for screening mammography. MATERIALS AND METHODS: A total of 198 English-speaking women, with no personal or family history of breast cancer, were recruited and randomized to four groups when they presented to the clinic for a screening mammogram. All women filled in a demographic data form and answered a questionnaire containing nine questions about breast cancer, risk, and screening to assess their knowledge and perception. Three educational interventions were tested in this study. The first consisted of a brochure, which provided answers to the questionnaire items and addressed the issues in more depth. The second intervention was an educational conversation with a specially trained mammography technologist. She reviewed the subject's answers to the questionnaire items correcting and/or clarifying them. The third intervention consisted of the brochure together with the conversation with a trained technologist. There was also a control group that just filled in the study questionnaire but did not receive an educational intervention. The same questionnaire was administered by telephone 4 to 6 weeks after the screening experience to all study subjects. Changes in their knowledge and perceptions of breast cancer were measured and compared. RESULTS: A statistically significant increase in knowledge was found in all of the three investigated groups compared to the control group. There were no statistically significant differences in the amount of increase between women who underwent different interventions. CONCLUSIONS: All three interventions resulted in increased knowledge about breast cancer and screening. No differences in the amount of knowledge increase were found between three interventions tested. The educational brochure seems to represent the most convenient and least costly method to increase knowledge about breast cancer and screening among women who present for screening mammography.

Low-Dose Gamma Knife Radiosurgery for Vestibular Schwannomas: Tumor Control and Cranial Nerve Function Preservation After 11 Gy.

OBJECTIVES: This study aims to report tumor control rates and cranial nerve function after low dose (11.0 Gy) Gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas. METHODS: A retrospective chart review was performed on 30 consecutive patients with vestibular schwannomas treated from March 2004 to August 2010 with GKRS at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The marginal dose for all patients was 11.0 Gy prescribed to the 50% isodose line. Median follow-up time was 42 months. The median treatment volume was 0.53 cm3. Hearing data were obtained from audiometry reports before and after radiosurgery. RESULTS: The actuarial progression free survival (PFS) based on freedom from surgery was 100% at 5 years. PFS based on freedom from persistent growth was 91% at 5 years. One patient experienced tumor progression requiring resection at 87 months. Serviceable hearing, defined as Gardner-Robertson score of I-II, was preserved in 50% of patients. On univariate and multivariate analyses, only higher mean and maximum dose to the cochlea significantly decreased the proportion of patients with serviceable hearing. CONCLUSION: Vestibular schwannomas can be treated with low doses (11.0 Gy) of GKRS with good tumor control and cranial nerve preservation.

Atypical meningioma: randomized trials are required to resolve contradictory retrospective results regarding the role of adjuvant radiotherapy.

BACKGROUND: The role of postoperative radiation (RT) in atypical meningioma remains controversial. MATERIALS AND METHODS: We report a retrospective review of outcomes and prognostic factor analysis in 158 patients treated between 2000 and 2010, and extensively review the literature. RESULTS: Following resection, 23 patients received immediate RT, whereas 135 did not. Median progression-free survival (PFS) with and without RT was 59 (range 43-86) and 88 (range 64-123) months. For Simpson grade (G) 1-3 resection, with and without RT, median PFS was 48 (2-80) versus 96 (88-123) months and for Simpson G4, it was 59 (6-86) versus 47 (15-104) months (P = 0.4). The rate of 5-year overall survival (OS) with and without RT was 89% and 83%, respectively. On univariate analysis, Simpson G4 (HR 3.2, P = 0.0006) and brain invasion (HR 2.2, P = 0.03) were significantly associated with progression, whereas age >60 years (HR 9.7, P = 0.002), mitoses >5 per 10 high-power field (0.2, P = 0.0056), and Simpson G4 (HR 2.4, P = 0.07) were associated with higher risk of death. We summarized 22 additional reports, which provide very divergent results regarding the benefit of RT. CONCLUSIONS: In our series, adjuvant RT is surprisingly associated with worse PFS and OS, and this is more likely to be due to selection bias of referring tumors with more aggressive characteristics such as elevated Ki-67 and brain invasion for adjuvant RT, rather than a direct causal effect of adjuvant RT. Although there is a trend toward improved PFS with adjuvant RT after subtotal resection, no improvement was noted in OS. Multivariate analysis did not yield statistical significance for any of the factors including Simpson grades of resection, adjuvant RT, or six pathological defining features. The relatively divergent results in the literature are most likely explained by patient selection variability; therefore, randomized trials to adequately address this question are clearly necessary.

A review of management strategies of malignant gliomas in the elderly population.

Glioblastoma Multiforme (GBM) is the most frequent primary malignant brain tumor in adults. It is an aggressive primary brain neoplasm, associated with a poor prognosis and median survival of less than 1 year. Approximately 50% of patients diagnosed with malignant gliomas in the United States are over the age of 65. Advancing age and poor performance status are two variables that have found to negatively affect prognosis. When compared to younger patients, not only is the treatment of elderly patients associated with decreased efficacy but also greater toxicity. As a result, elderly patients often receive less aggressive treatment and are excluded from clinical trials. There are many challenges in the treatment of elderly patients with GBM including increased surgical morbidity and mortality as well as increased toxicity to radiation and chemotherapy. As such, the optimal therapy remains unclear and controversial for the elderly malignant glioma population.

Effect of recombinant human deoxyribonuclease on oropharyngeal secretions in patients with head-and-neck cancers treated with radiochemotherapy.

PURPOSE: The current study examined the effect of recombinant human deoxyribonuclease (rhDNase) on quality of life (QOL) measures, clinical improvement, and DNA content of thick oropharyngeal secretions (OPS) in patients with head-and-neck (H&N) cancers. METHODS AND MATERIALS: Thirty-six patients with local-regional advanced H&N cancer receiving chemoradiationtherapy (CRT) were randomized to receive either placebo or rhDNase. Endpoints included MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-NH) scores, along with clinical assessment and DNA concentration of OPS. RESULTS: There were no statistically significant differences in patients' QOL outcomes over the study period. Both groups showed an increase in symptom and interference scores, although patients in the rhDNase group showed a greater decline in both scores during the 3 months posttreatment. Similarly, both groups showed a decline in physical and functional well being but recovered in the 3 months posttreatment follow-up, with the rhDNase group exhibiting speedier recovery. Patients in the rhDNase group exhibited significant clinical improvement in OPS, blindly assessed by a physician, compared with the placebo group (67% vs 27%, respectively; P=.046). The rhDNase group showed no change in OPS-DNA concentration, although the placebo group showed a significant increase in DNA concentration during the drug trial (P=.045). There was no differences in acute toxicities between the 2 groups. CONCLUSIONS: Our preliminary data suggest that rhDNase did not significantly improve study primary endpoints of QOL measures compared with the placebo group. However, there was a significant improvement in secondary endpoints of clinically assessed OPS and DNA concentration compared with placebo in H&N cancer patients treated with CRT. Further investigation in larger numbers of patients is warranted.

Using intensity-modulated radiotherapy to spare the kidney in a patient with seminoma and a solitary kidney: a case report.

AIMS AND BACKGROUND: Radiotherapy-related kidney injury is multifactorial and influenced by radiation dose-volume distributions, patient-related factors, and chemotherapy. Traditional radiation parameters for the kidney are based on pre-intensity-modulated radiotherapy (IMRT) data and focus on limiting the volume receiving high dose. We report a case of testicular seminoma with paraaortic adenopathy in a patient with a solitary kidney treated with radiotherapy. METHODS: A comparison was performed for IMRT and two 3D-conformal techniques. In our case, IMRT reduced the volume of kidney receiving high dose but increased the volume receiving low dose. RESULTS: Given the lack of data for suggesting that large renal volumes treated to low doses would cause excess toxicity, the consensus opinion was to proceed with IMRT. The patient tolerated treatment well without evidence of radiotherapy-related kidney injury. CONCLUSIONS: As patients are treated with increasingly complex techniques such as IMRT, understanding low dose effects and monitoring low dose parameters may become clinically important.

Adaptive radiotherapy for head and neck cancer--dosimetric results from a prospective clinical trial.

PURPOSE: To conduct a clinical trial evaluating adaptive head and neck radiotherapy (ART). METHODS: Patients with locally advanced oropharyngeal cancer were prospectively enrolled. Daily CT-guided setup and deformable image registration permitted mapping of dose to avoidance structures and CTVs. We compared four planning scenarios: (1) original IMRT plan aligned daily to marked isocenter (BB); (2) original plan aligned daily to bone (IGRT); (3) IGRT with one adaptive replan (ART1); and (4) actual treatment received by each study patient (IGRT with one or two adaptive replans, ART2). RESULTS: All 22 study patients underwent one replan (ART1); eight patients had two replans (ART2). ART1 reduced mean dose to contralateral parotid by 0.6 Gy or 2.8% (paired t-test; p=0.003) and ipsilateral parotid by 1.3 Gy (3.9%) (p=0.002) over the IGRT alone. ART2 further reduced the mean contralateral parotid dose by 0.8 Gy or 3.8% (p=0.026) and ipsilateral parotid by 4.1 Gy or 9% (p=0.001). ART significantly reduced integral body dose. CONCLUSIONS: This pilot trial suggests that head and neck ART dosimetrically outperforms IMRT. IGRT that leverages conventional PTV margins does not improve dosimetry. One properly timed replan delivers the majority of achievable dosimetric improvement. The clinical impact of ART must be confirmed by future trials.

Dosimetric changes resulting from patient rotational setup errors in proton therapy prostate plans.

PURPOSE: To evaluate the dose changes to the target and critical structures from rotational setup errors in prostate cancer patients treated with proton therapy. METHODS AND MATERIALS: A total of 70 plans were analyzed for 10 patients treated with parallel-opposed proton beams to a dose of 7,600 (60)Co-cGy-equivalent (CcGE) in 200 CcGE fractions to the clinical target volume (i.e., prostate and proximal seminal vesicles). Rotational setup errors of +3 degrees , -3 degrees , +5 degrees , and -5 degrees (to simulate pelvic tilt) were generated by adjusting the gantry. Horizontal couch shifts of +3 degrees and -3 degrees (to simulate longitudinal setup variability) were also generated. Verification plans were recomputed, keeping the same treatment parameters as the control. RESULTS: All changes shown are for 38 fractions. The mean clinical target volume dose was 7,780 CcGE. The mean change in the clinical target volume dose in the worse case scenario for all shifts was 2 CcGE (absolute range in worst case scenario, 7,729-7,848 CcGE). The mean changes in the critical organ dose in the worst case scenario was 6 CcGE (bladder), 18 CcGE (rectum), 36 CcGE (anterior rectal wall), and 141 CcGE (femoral heads) for all plans. In general, the percentage of change in the worse case scenario for all shifts to the critical structures was <5%. Deviations in the absolute percentage of volume of organ receiving 45 and 70 Gy for the bladder and rectum were <2% for all plans. CONCLUSION: Patient rotational movements of 3 degrees and 5 degrees and horizontal couch shifts of 3 degrees in prostate proton planning did not confer clinically significant dose changes to the target volumes or critical structures.

Intra-operative pubic arch interference during prostate seed brachytherapy in patients with CT-based pubic arch interference of < or =1cm.

PURPOSE: There are only a few reports on the frequency of intra-operative pubic arch interference (I-PAI) during prostate seed brachytherapy (PB). MATERIALS AND METHODS: Two hundred and forty-three patients with a CT-based pubic arch interference (PAI) of < or =1 cm and a prostate volume of < or =50-60 cc underwent PB. Those patients requiring needle repositioning by > or =0.5 cm on the template were scored as having I-PAI. The incidence of I-PAI and its impact on biochemical control were analyzed. RESULTS: Intra-operative PAI was encountered in 47 (19.3%) patients. Forty two patients (17.3%) had I-PAI in 1-2 needles, two (0.8%) had I-PAI in four needles and three patients (1.2%) had I-PAI in six needles. Overall, 1.4% of needles required repositioning due to I-PAI. BMI>27 kg/m(2) and wider (>75 mm) pubic bone separation at mid ramus (PS-ML) were associated with a lower incidence of I-PAI. At a median follow-up of 50.1 months, the 3- and 5-year bPFS was 97.3% and 95.2%, respectively. The 5-year bPFS rates for patients with and without I-PAI were 95.6% and 95%, respectively (p=0.28). CONCLUSIONS: The use of CT-based PAI of < or =1cm as a selection criterion for PB is a simple and reliable method for minimizing the incidence of I-PAI and maintaining excellent biochemical control rates.

Palliative radiation therapy in the management of brain metastases, spinal cord compression, and bone metastases.

Radiation therapy plays an important role in both curative and palliative cancer treatment. Palliative radiation therapy is given to alleviate symptoms, restore function, relieve suffering caused by cancer, and improve quality of life. Pain relief, control of bleeding or ulceration, prevention of impending compression or obstruction from tumor, and shrinkage of tumor masses causing symptoms are indications for palliative radiotherapy. Palliative radiotherapy is a very effective tool in alleviating pain symptoms and generally well tolerated. Common fractionation schemes are 8 Gy delivered in one fraction and 30 Gy delivered in 10 fractions. This article discusses general principles of administering palliative radiation therapy. Site-specific treatment is addressed, divided into palliative radiotherapy for brain metastases, spinal cord compression, and bone metastases. In each of these areas, we discuss presentation, management, and therapeutic strategies.