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Purpose/Objective(s) To determine if hypofractionated post-operative prostate bed radiotherapy (HYPORT) does not increase patient-reported genitourinary (GU) or gastrointestinal (GI) toxicity over conventionally fractionated post-operative radiotherapy (COPORT). Materials/Methods Eligibility criteria were: 1) an undetectable PSA ( Results Between July 2017 and July 2018, 298 patients were screened and 296 were randomized: 144 to HYPORT and 152 to COPORT. Compliance with the EPIC was 100% at baseline, 83% at the end of RT, 77% at 6 months, 78% at 12 months, and 73% at 24 months. At the end of RT, the HYPORT and COPORT mean GU change scores were neither clinically significant nor significantly different and remained so at 6 and 12 months. The mean GI change scores for HYPORT and COPORT were both clinically significant and significantly different at the end of RT (HYPORT mean GI = -15.0 vs COPORT mean GI = -6.8 P ≤ 0.01). However, both the HYPORT and COPORT mean GI change scores clinically and statistically significant differences were resolved at 6 and 12 months. The 24-month mean GU and GI change scores for HYPORT and COPORT remained neither clinically nor statistically significant (HYPORT mean GU = -5.2 vs COPORT mean GU = -3.0, P = 0.81; HYPORT mean GI = -2.2 vs COPORT mean GI = -1.5, P = 0.12). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT versus COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount (2-yr actuarial, 12% vs 8%, P = 0.29) or local failure (2-yr actuarial, 0.7% vs 0.8%, P = 0.35). Conclusion HYPORT is non-inferior to COPORT in terms of late patient-reported GU or GI toxicity. More follow-up is needed to appropriately assess disease control endpoints. In some clinic scenarios, HYPORT may be considered an acceptable practice standard.

While some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible.We identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1-2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost.The median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13-$19,863.03, p0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14-$29,511.16, p0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p0.001).MRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application.

Introduction The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. Methods NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1–4N0–1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. Results This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2–9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3–51.0) and 31.7% (95% CI: 18.3–46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3–74.4) and 46.7% (95% CI: 21.2–68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. Conclusions The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach.

Purpose Incidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. Methods and Materials Bowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. Results Interfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. Conclusions In the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.

Introduction et but de l’etude La radiotherapie externe avec chimiotherapie concomitante (5-fluoro-uracile–mitomycine C) est le traitement de reference du cancer de canal anal. Une analyse des donnees de sept essais a ete faite pour quantifier l’effet des parametres relie avec la radiotherapie externe sur les resultats therapeutiques. Materiel et methodes Apres fusion des jeux de donnees l’impact des parametres de radiotherapie (etalement, duree de l’intervalle de temps, dose totale) sur les resultats therapeutiques (recidive locoregionale, taux de survie sans progression a 5 ans et toxicite) ont ete evalues. Les donnees ont ete recues de dix essais publies sur 13, realises entre 1987 et 2008 (n = 3031). Une regression de Cox a ete utilisee. Resultats et analyse statistique Seuls les dossiers de 1343 patients des sept essais plus recents et homogenes ont ete analyses (duree mediane de suivi :4,1 ans). Un taux superieur de recidive locoregionale a 5 ans avait une correlation significative avec un etalement plus long (22,8 %, intervalle de confiance a 95 % [IC 95 %] : 22,3–27,3 %, p = 0,030), une taille tumorale superieure (p 79,3 % ; p Conclusion Pour des patients pris en charge par chimioradiotherapie concomitante par deux agents et une radiotherapie externe, un etalement plus long semble desavantageux. De futurs essais avec des techniques modernes pourraient mieux definir l’etalement optimal et le role de l’escalade de dose.

Introduction: Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy iso- flavones in the radioprotection of lung tissue. Methods: Naive Balb/c mice were treated with oral soy isoflavones for 3 days before and up to 4 months after radiation. Radiation was administered to the left lung at 12 Gy. Mice were monitored for toxic- ity and breathing rates at 2, 3, and 4 months after radiation. Lung tis- sues were processed for histology for in situ evaluation of response. Results: Radiation caused damage to normal hair follicles, leading to hair loss in the irradiated left thoracic area. Supplementation with soy isoflavones protected mice against radiation-induced skin injury and hair loss. Lung irradiation also caused an increase in mouse breathing rate that was more pronounced by 4 months after radia- tion, probably because of the late effects of radiation-induced injury to normal lung tissue. However, this effect was mitigated by soy isoflavones. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving alveoli and bronchioles and a progressive increase in fibrosis. These adverse effects of radia- tion were alleviated by soy isoflavones. Conclusion: Soy isoflavones given pre- and postradiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective effect of soy.

Purpose The purpose of this study was to identify factors associated with cardiac toxicity in patients treated with chemoradiation therapy (CRT) for esophageal carcinoma. Methods and Materials One hundred twenty-seven patients with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July 2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT were retrospectively reviewed. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass and angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor location. T test assessed risk of cardiac toxicity secondary to age. Dose volume histograms (DVH) were evaluated for percentage of heart volume receiving >20, 30, 40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association between dose volume parameters and cardiac toxicity. Results Patient population included 100 men and 27 women with a mean age of 64 years. Median follow-up was 12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28 patients, the majority of which were pericardial effusion (23/28). Odds ratio for toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017) and time to cardiac toxicity by sex was significant (P = .0003). Patients above the median cutoff for V20, V30, and V40 had increased odds of developing cardiac toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing cardiac toxicity with V40 >57% (95% CI, 1.5-10.3, P = .002). On multivariable logistic regression analysis, sex was the only variable associated with any cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the other investigated variables were associated with increased risk of cardiac toxicity. Conclusions Female patients and dose greater than the median for V20-V40 were associated with the development of cardiac toxicity, specifically pericardial effusion. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial effusion may be a long-term complication.

Increased consumption of cruciferous vegetables is associated with decreased risk in prostate cancer (PCa). The active compound in cruciferous vegetables appears to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3-carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in a Phase I trial in PCa. We investigated the anti-cancer activity of B-DIM as a new biological approach to improve the effects of radiotherapy for hormone refractory prostate cancer cells, which were either positive or negative for androgen receptor (AR) expression. B-DIM inhibited cell growth in a dose-dependent manner in both PC-3 (AR-) and C4-2B (AR+) cell lines. B-DIM was effective at increasing radiation-induced cell killing in both cell lines, independently of AR expression. B-DIM inhibited NF-κB and HIF-1α DNA activities and blocked radiation-induced activation of these transcription factors in both PC-3 and C4-2B cells. In C4-2B (AR+) cells, AR expression and nuclear localization were significantly increased by radiation. However, B-DIM abrogated the radiation-induced AR increased expression and trafficking to the nucleus, which was consistent with decreased PSA secretion. In vivo, treatment of PC-3 prostate tumors in nude mice with B-DIM and radiation resulted in significant primary tumor growth inhibition and control of metastasis to para-aortic lymph nodes. These studies demonstrate that B-DIM augments radiation-induced cell killing and tumor growth inhibition. B-DIM impairs critical survival signaling pathways activated by radiation, leading to enhanced cell killing. These novel observations suggest that B-DIM could be used as a safe compound to enhance the efficacy of radiotherapy for castrate-resistant PCa.

Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.

We have demonstrated that soy isoflavones radiosensitize cancer cells. Prostate cancer patients receiving radiotherapy (RT) and soy tablets had reduced radiation toxicity to surrounding organs. We have now investigated the combination of soy with RT in lung cancer (NSCLC), for which RT is limited by radiation-induced pneumonitis.Human A549 NSCLC cells were injected i.v. in nude mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with left lung RT at 12 Gy and with oral soy treatments at 1mg/day for 30 days. Lung tissues were processed for histology.Compared to lung tumor nodules treated with soy isoflavones or radiation, lung tissues from mice treated with both modalities showed that soy isoflavones augmented radiation-induced destruction of A549 lung tumor nodules leading to small residual tumor nodules containing degenerating tumor cells with large vacuoles. Soy isoflavones decreased the hemorrhages, inflammation and fibrosis caused by radiation in lung tissue, suggesting protection of normal lung tissue.Soy isoflavones augment destruction of A549 lung tumor nodules by radiation, and also mitigate vascular damage, inflammation and fibrosis caused by radiation injury to normal lung tissue. Soy could be used as a non-toxic complementary approach to improve RT in NSCLC.

Purpose To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. Methods and Materials A systematic search of the National Library of Medicine’s PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. Results The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. Conclusions Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation.

Purpose The specific aim of this analysis was to evaluate the feasibility of performing a cost-effectiveness analysis using Medicare data from patients treated on a randomized Phase III clinical trial. Methods and Materials Cost data included Medicare Part A and Part B costs from all providers—inpatient, outpatient, skilled nursing facility, home health, hospice, and physicians—and were obtained from the Centers for Medicare & Medicaid Services for patients eligible for Medicare, treated on Radiation Therapy Oncology Group (RTOG) 9111 between 1992 and 1996. The 47-month expected discounted (annual discount rate of 3%) cost for each arm of the trial was calculated in 1996 dollars, with Kaplan-Meier sampling average estimates of survival probabilities for each month and mean monthly costs. Overall and disease-free survival was also discounted 3%/year. The analysis was performed from a payer's perspective. Incremental cost-effectiveness ratios were calculated comparing the chemotherapy arms to the radiation alone arm. Results Of the 547 patients entered, Medicare cost data and clinical outcomes were available for 66 patients. Reasons for exclusion included no RTOG follow-up, Medicare HMO enrollment, no Medicare claims since trial entry, and trial entry after 1996. Differences existed between groups in tumor characteristics, toxicity, and survival, all which could affect resource utilization. Conclusions Although we were able to test the methodology of economic analysis alongside a clinical trial using Medicare data, the results may be difficult to translate to the entire trial population because of non-random missing data. Methods to improve Medicare data capture and matching to clinical trial samples are required.

*Fox Chase Cancer Center, Philadelphia, PA; yUniversity of Texas, MD Anderson Cancer Center, Houston, TX; zCancer Institute of New Jersey, New Brunswick, NJ; {Saint Barnabas Health Care System, Toms River, NJ; xH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; **Mayo Clinic and Mayo Foundation, Rochester, MN; yyUniversity of Colorado Health Services, Boulder, CO; {{University of Wisconsin, Madison, WI; xxWayne State University School of Medicine, Detroit, MI; and ***21st Century Oncology, Inc, Moorestown, NJ.

Low anterior resection or abdominoperineal resection is considered standard treatment for early rectal cancer. These procedures, however, carry a risk of morbidity and mortality that may not be warranted for early distal lesions, which may be treated with local excision. Emerging data has investigated the efficacy of local excision in patients with early stage rectal cancers. An expert panel designated by the American College of Radiology has reviewed supporting data, from a few prospective multi-institutional trials and a number of single-institution, retrospective reviews. The consensus recognizes the importance of accurate staging to identify patients who may be candidates for a local excision approach. Optimal candidates for local excision alone include small, low-lying T1 tumors, without adverse pathologic features. A number of procedures may be safely used including transanal, posterior trans-sphincteric, posterior proctotomy, transanal excision, or transanal microsurgery. It is important to note that none of these include lymph node evaluation, and depending on the risk of lymph node metastases, adjuvant radiation with or without chemotherapy may be warranted. Patients with positive margins or T3 lesions are at high risk of local recurrence and should be offered immediate APR or LAR. However, patients with high-risk T1 tumors, T2 tumors, or those who are not amenable to more radical surgery may benefit from adjuvant treatment. Data have also reported excellent local control rates for neoadjuvant radiation +/- chemotherapy followed by local excision in higher risk patients, but it is not yet clear if this approach reduces recurrence rates over surgery alone.

s Korean Institute of Radiological and Medical Sciences. Forty-four patients received 32–36 Gy in 4 fractions, with the exception of 1 patient who received 24 Gy in 3 fractions (49, 50). There were 10 low-risk (PSA

Purpose To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up. Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.

As health care spending in the United States continues to increase at a pace significantly faster than that of other sectors of the economy, there seems to be greater interest and willingness to consider the root causes of the rise and to explore options for reform. Some of the reasons for cost escalation are associated with a growing and aging population that all too often makes inappropriate personal choices, but others are clearly attributable to growth in the cost of drugs, hospital and nursing home care, provider reimbursement, and durable medical equipment. Some health care economists have suggested that the rapid introduction of new technologies has also played a major role. Vendors understandably desire early market penetration of any new device or technology, but often this may be accomplished before significant evidence of benefit is available. Our current system of device approval unlinked to coverage and payment has produced further disruption in the system. The nature of the problem and consideration of various factors in the introduction, implementation, and evaluation of new technologies will be considered.

The American College of Radiology (ACR) Appropriateness Criteria ® on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology–Rectal/Anal Cancer, based on a literature review completed in 2007.

Background For patients with borderline resectable pancreatic cancer, preoperative chemoradiation and standalone chemotherapy may allow for R0 resection and improved survival. Methods A retrospective review of patients with borderline resectable pancreatic cancer treated with preoperative chemoradiation and standalone chemotherapy was undertaken. Clinical variables, including disease-free and overall survival, were collected. Univariate analysis was used to identify factors impacting survival. Results Thirteen patients with borderline resectable pancreatic cancer were treated with preoperative chemoradiation and chemotherapy. Morbidity and mortality were 38% and 0. There were 2 R1 and 11 R0 resections. Nine patients are alive with a median follow-up of 20 months. Five patients recurred at a median of 4 months. Tumor fibrosis ≤60% was associated with recurrence and poor survival. Conclusions Preoperative chemoradiation and chemotherapy allow a select group of patients with borderline resectable pancreatic cancer to undergo an R0 or R1 resection with acceptable morbidity and mortality. Tumor response may be associated with survival.

Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS).Methods and Materials: HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model.Results: Baseline FACT-H&N data were available for 1,093 patients and missing for 417 patients. No significant difference in outcome was found between the patients with and without baseline FACT-H&N data (p = 0.58). The median follow-up time was 27.2 months for all patients and 49 months for surviving patients. Multivariate analyses were performed for both OS and LRC. Beyond tumor and nodal stage, Karnofsky performance status, primary site, cigarette use, use of concurrent chemotherapy, and altered fractionation schedules, the FACT-H&N score was independently predictive of LRC (but not OS), with p = 0.0038. The functional well-being component of the FACT-H&N predicted most significantly for LRC (p = 0.0004).Conclusions: This study represents, to our knowledge, the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients. The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer. (C) 2008 Elsevier Inc.

Purpose To determine whether 18-fluorodeoxyglucose positron emission tomography (PET) computed tomography scans predict the pathologic complete response and disease-free and overall survival in patients with esophageal carcinoma undergoing definitive or preoperative chemoradiotherapy. Methods and Materials The records of patients with esophageal carcinoma presenting for definitive or preoperative treatment and undergoing pre- and post-treatment 18-fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed. The histologic type, T stage, and nodal status were the variables investigated to determine a relationship with the baseline standardized uptake value (SUV) of the primary tumor at diagnosis. We also attempted to determine whether a relationship exists between the percent decrease in SUV and a pathologic complete response, overall and disease-free survival. Results A total of 81 patients, 14 women and 67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before treatment and 63 also had post-treatment scans. T stage and tumor location predicted in univariate, but not multivariate, analysis for the initial SUV. Of the patients with a postchemoradiotherapy SUV of p = 0.09 and p = 0.08, respectively). The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group ( p = 0.01). Conclusions A correlation was found between the depth of tumor invasion and the baseline SUV. The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group. Caution should be exercised in using post-treatment PET scans to determine the necessity for surgical resection.

Anal cancer is a relatively rare neoplasm, accounting for roughly 4,500 cases per year. The evolution of the definitive treatment of anal cancer from a surgical to a nonsurgical approach, however, has been viewed as a model disease site in a larger paradigm shift in medicine. Organ preservation, in this case a functional anal sphincter, and durable cure are obtainable goals. To this end, anal cancer is a disease best treated primarily with chemoradiation. Although appropriate treatment can produce acceptable results, further investigation and improvement in therapy are still needed.

Purpose: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. Methods and Materials: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age ≥18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m 2 twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. Results: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity—six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. Conclusion: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.

The specific aim of this study was to evaluate outcome differences by gender and partner status for patients treated on Radiation Therapy Oncology Group (RTOG) protocol 97-14.RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Retreatment rates and overall survival were made based upon gender, marital status, and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate retreatment time at 36 months from enrollment, and Gray's test was used to test for treatment differences within the same groupings. Marital status, gender, KPS, and treatment were variables tested in a univariate Cox model evaluating the time to retreatment.Married men and women and single women receiving 30 Gy had significantly longer time to retreatment, p = 0.0067, p = 0.0052, and p = 0.0009 respectively. We failed to show a difference in retreatment rates over time in single men receiving either 30 Gy or 8 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive retreatment, p0.0001, with a trend toward single patients less likely to be re-treated, p = 0.07.Non-disease-related variables, such as social support, might influence the results of clinical trials with subjective endpoints such as retreatment rates. The statistically nonsignificant difference in the 36-month retreatment rates observed in single male patients receiving 8 Gy may be a result of inadequate social support systems in place to facilitate additional care. Patients receiving 8 Gy in a single fraction had significantly higher retreatment rates compared with patients receiving 30 Gy in 10 fractions.

Purpose: The α/β ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. Patients and Methods: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. Results: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. Conclusion: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. This approach may be associated with higher complication rates. A large single-center experience was reviewed to determine whether induction CRT was associated with increased morbidity and mortality among 179 patients undergoing esophagectomy between January 1994 and December 2002. Morbidity was recorded as any complication requiring additional intervention. Mortality was defined as patient death within the first 30 postoperative days or death during the initial hospitalization. In total, 131 patients underwent induction CRT followed by surgery. The most common operation was an Ivor-Lewis esophagogastrectomy (60%). Median survival of the entire group was 33 months and 5-year survival was 26%. Perioperative mortality was 5% and did not differ between induction (4.6%) and non-induction (6.3%) groups. The overall complication rate was 57%, reflecting a very liberal definition of postoperative complications. There were no differences between the two groups in terms of such major complications as anastomotic leak, pneumonia, acute respiratory distress syndrome, respiratory failure, chylothorax, atrial arrhythmia, and wound infections. There were only two complications that occurred more frequently in the induction group--venous thrombosis (8.4% v 0%) and vocal cord paresis (7.6% v 2.1%). The median hospital stay was similar in patients who had complications versus those who did not (12 v 13 days) and in patients who underwent induction CRT versus those that did not (12 days v 13.5 days). Esophagectomy can be performed safely with low mortality and acceptable morbidity following neoadjuvant chemotherapy and radiation with no increase in hospital stay for patients with complications.

Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138–$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47–5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058–$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42–6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.

Purpose: To perform a systematic review of the evidence to determine the efficacy and effectiveness of three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer; provide a clear presentation of the key clinical outcome questions related to the use of 3D-CRT in the treatment of localized prostate cancer that may be answered by a formal literature review; and provide concise information on whether 3D-CRT improves the clinical outcomes in the treatment of localized prostate cancer compared with conventional RT. Methods and Materials: We performed a systematic review of the literature through a structured process developed by the American Society for Therapeutic Radiology and Oncology’s Outcomes Committee that involved the creation of a multidisciplinary task force, development of clinical outcome questions, a formal literature review and data abstraction, data review, and outside peer review. Results: Seven key clinical questions were identified. The results and task force conclusions of the literature review for each question are reported. Conclusion: The technological goals of reducing morbidity with 3D-CRT have been achieved. Randomized trials and follow-up of completed trials remain necessary to address these clinical outcomes specifically with regard to patient subsets and the use of hormonal therapy.

Radiation is an effective modality to aid in symptom management of patients with metastatic disease. The type and duration of treatment depends on the Karnofsky performance status (KPS) of the patient and type and status of the cancer. Abbreviated treatment regimens may be favored in this patient population. They provide quick palliation without the patient and family spending significant time traveling back and forth to the treatment center. Hypofractionated regimens have been found effective in relieving pain from metastatic bone disease, relieving obstruction from locally advanced lung cancer, bleeding from gynecologic cancers, and hematuria from advanced bladder cancer. More aggressive regimens such as whole-brain radiation therapy (WBRT) and stereotactic radiosurgery may be appropriate for select patients with a good KPS. Radiation has also been found to be effective in palliating recurrent cancer that has already received definitive radiation.

Purpose Accurate delineation of the gross tumor volume (GTV) is important in radiation therapy treatment planning. We evaluated the impact of PET and endoscopic ultrasound (EUS) compared with CT simulation in the planning of radiation fields for patients with esophageal carcinoma. Material and methods Twenty-five patients presenting with esophageal carcinoma for radiation therapy underwent PET scans in the treatment position after conventional CT simulation. Patients underwent PET/CT scanning after being injected with 10 to 20 mCi of [F-18]-2-deoxy-2-fluro-d-glucose. The length of the abnormality seen on the CT portion of the PET/CT scan vs. the PET scan alone was determined independently by 2 separate investigators. The length of the GTV and detection of regional adenopathy by PET was also correlated with EUS in 18 patients. Of the 18 patients who had EUS, 2 had T2 tumors and 16 had T3 tumors. Eighteen patients had adenocarcinoma and 7 had squamous cell carcinoma. Nine tumors were located at the gastroesophageal junction, 8 at the lower esophagus, 7 in the middle esophagus, and 1 in the cervical esophagus. The PET scans were reviewed to determine the length of the abnormality by use of a standard uptake value (SUV) of 2.5 to delineate the tumor extent. Results The mean length of the cancer was 5.4 cm (95% CI 4.4–6.4 cm) as determined by PET scan, 6.77 cm (95% CI, 5.6–7.9 cm) as determined by CT scan, and 5.1 cm (95% CI, 4.0–6.1 cm) for the 22 patients who had endoscopy. The length of the tumors was significantly longer as measured by CT scans compared with PET scans ( p = 0.0063). EUS detected significantly more patients with periesophageal and celiac lymphadenopathy compared to PET and CT. The SUV of the esophageal tumors was higher in patients with peri-esophageal lymphadenopathy identified on PET scans. Conclusion Endoscopic ultrasound and PET scans can add additional information to aid the radiation oncologist's ability to precisely identify the GTV in patients with esophageal carcinoma.

Background To evaluate the various treatments for patients with hormone-refractory prostate cancer with bone metastases using a Markov model. Methods and materials The base case to be evaluated was of a man with hormone-refractory prostate cancer. The evaluated palliative treatments were pain medication only, chemotherapy consisting of mitoxantrone and prednisone, and single- and multifraction radiotherapy (RT). A literature search was used to generate the transition probabilities and patient utilities. Modeling was used to generate the cost estimates. Expert opinion was used to generate utilities and cost estimates in the absence of literature data. Second-order Monte Carlo simulation produced incremental cost-effectiveness scatterplots and 95% confidence ellipses. Results Pain medication had the least expected mean cost of all the treatment options at $11,700 but also the second lowest quality-adjusted survival at 5.75 quality-adjusted life months. Chemotherapy had the highest expected mean cost, $15,300, but the lowest quality-adjusted life months (4.93). Incremental cost-effectiveness analysis revealed that single-fraction RT was the most cost-effective treatment, with a cost of $6857/quality-adjusted life year; multifraction RT had an incremental cost-effectiveness ratio of $36,000/quality-adjusted life year. Chemotherapy was dominated by pain medication. Conclusion Within the limits of the established model, single-fraction RT was the most cost-effective palliative treatment compared with pain medication, chemotherapy, and multifraction RT. The use of this model allowed comparison of different treatment regimens that could never be evaluated together in a randomized clinical trial.

Purpose: To ( 1 ) measure radiation therapy costs for patients in randomized controlled clinical trials, ( 2 ) compare measured costs to modeling predictions, ( 3 ) examine cost distributions, and ( 4 ) assess feasibility of collecting economic data within a cooperative group. Methods: The Radiation Therapy Oncology Group conducted economic pilot studies for two Phase III studies that compared fractionation patterns. Expected quantities of Current Procedural Terminology (CPT) codes and relative value units (RVU) were modeled. Institutions retrospectively provided procedure codes, quantities, and components, which were converted to RVUs used for Medicare payments. Cases were included if the radiation therapy quality control review judged them to have been treated per protocol or with minor variation. Cases were excluded if economic quality review found incomplete economic data. Results: The median and mean RVUs were within the range predicted by the model for all arms of one study and above the predicted range for the other study. Conclusion: The model predicted resource use well for patients who completed treatment per protocol. Actual economic data can be collected for critical cost items. Some institutions experienced difficulty collecting retrospective data, and prospective collection of data is likely to allow wider participation in future Radiation Therapy Oncology Group economic studies.

To perform a cost-utility analysis utilizing a cooperative group protocol and constrasting the results with the published quality adjusted survival.A cost-utility analysis was performed on Radiation Therapy Oncology Group (RTOG) protocol 83-02. The quality-adjusted survival has been published previously. Pretreatment tests and chemotherapy costs are not considered, as these were similar across all treatment arms. Payor costs are calculated from Federal Register data for Medicare Region IV. Global charges are used to calculate the professional and technical charges. Costs are measured in relative value units (RVUs) and are tabulated assuming equal treatment complexity for all treatment arms.The number of RVUs calculated for each arm were 48 Gy--166.65; 54.4 Gy--182.17; 64.8 Gy--232.53; 72.0 Gy--272.19; 76.8 Gy--287.11; and 81.6 Gy--302.63. The RVU/QALY for the50-year-old group were 48 Gy--119.03; 54.4 Gy--100.65; 64.8 Gy--104.78; 72.0 Gy--90.73; 76.8 Gy--193.99; and 81.6 Gy--165.37. The RVU/QALY for the50-year-old group were 48 Gy--198.39; 54.4 Gy--276.85; 64.8 Gy--426.57; 72.0 Gy--423.71; 76.8 Gy--703.70; and 81.6 Gy--519.10. Sensitivity analysis of one treatment plan, simulation, and set of blocks for the 48 Gy and 54.4 Gy arms decreased the RVU/QALY to 105.34 and 90.05, respectively.Our analyses shows the experimental arm with the lowest RVU/QALY is also the arm with the longest quality-adjusted survival. This arm had the most efficient use of resources in this protocol. Prospective collection of all pertinent cost data is required for comparison of one treatment against another. All cooperative group protocols should have prospective quality of life and economic endpoints to allow for comparison of the most cost efficient treatment method.

Purpose: To investigate the incidence and etiologic factors of pelvic fractures following radiation therapy for endometrial carcinoma. Methods and Materials: Tumor registry and radiation oncology records of patients treated for endometrial carcinoma at The Toledo Hospital between April 1989, and December 1992, were reviewed. Patients identified as having pelvic fractures without the presence of metastatic disease underwent total body mineral density measurement with dual x-ray densitometry. Results: Two of 75 patients (2.7%) were found to have pelvic fractures an average of 29 months from the completion of postoperative irradiation. One patient, who received preoperative irradiation, was also identified as having developed a fracture of the pelvis and was included in the analysis. All patients were treated prone with 10–15 MV photons in four fields daily. All three fracture patients received 45 Gy external beam radiation therapy. The two postoperative patients each received a single vaginal brachytherapy application delivering 20 Gy to 0.5 cm deep to the vaginal mucosa with a vaginal cylinder containing 30 mgRaeq 137 Cs. The preoperative patient received a single brachytherapy application with tandem and colpostats delivering 20 Gy to point A. Only one of the three fracture patients had the entire pubis included in the field of external beam treatment. One patient was taking nonsteroidal anti-inflammatory medication, one patient thyroid hormone replacement, and one patient was taking both types of medication. Conclusion: The etiology of pelvic fractures after irradation is multifactorial. A complete medication history should be obtained, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the iniation of the radiation treatment.