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Purpose Recently, involved-site radiation therapy (ISRT) guidelines have been developed and published to replace the previous concept of involved-field radiation therapy for patients with lymphoma. However, these ISRT guidelines may be interpreted in different ways, posing difficulties for prospective clinical trials. This study reports survey results regarding interpretation of the ISRT guidelines. Methods and Materials Forty-four expert lymphoma radiation oncologists were asked to participate in a survey that included 7 different cases associated with 9 questions. The questions pertained to ISRT contouring and asked respondents to choose between 2 different answers (no “correct” answer) and a third write-in option allowed. Results Fifty-two percent of those surveyed responded to the questionnaire. Among those who responded, 72% have practiced for >10 years, 46% have treated >20 Hodgkin lymphoma cases annually, and 100% were familiar with the ISRT concept. Among the 9 questions associated with the 7 cases, 3 had concordance among the expert radiation oncologists of greater than 70%. Six of the questions had less than 70% concordance (range, 56%-67%). Conclusions Even among expert radiation oncologists, interpretation of ISRT guidelines is variable. Further guidance for ISRT field design will be needed to reduce variability among practicing physicians.

Standard of care treatment for pediatric patients with stage III Hodgkin lymphoma (HL) is chemotherapy with involved-field radiotherapy (IFRT) reserved for patients receiving less-intensive chemoth...

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Crohn's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies > 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p < 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men < 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p < 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.

Hodgkin lymphoma and non-Hodgkin lymphoma are common hematologic malignancies with such a favorable prognosis that many survivors live decades after combined chemotherapy and radiotherapy. These survivors, however, are at risk of developing late treatment adverse effects from collateral damage, including secondary malignancies, cardiac toxicities, and ischemic heart diseases. Recent efforts have successfully reduced the radiation dose and treatment field without compromising cure rates. Proton therapy has the potential of further lowering the treatment-related toxicity owing to its ability to deposit a high dose only at the target. Although this finding has been supported by several current dosimetric studies, its utilization in the management of lymphoma has been limited during the past 5 years because of the paucity of facilities and the difficulty of obtaining insurance coverage. With diligent follow-up, the clinical impact of proton therapy will be established to improve the therapeutic ratio and to reduce late treatment-related morbidity.

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

The main objectives of follow-up studies after completion of treatment for Hodgkin lymphoma are detection of recurrence for salvage therapy and monitoring for sequelae of treatment. The focus of the follow-up shifts, with time after treatment, from detection of recurrence to long-term sequelae. A majority of recurrence is detected by history and physical examination. The yield for routine imaging studies and blood tests is low. Although routine surveillance CT scan can detect recurrence not detected by history and physical examination, its benefit in ultimate survival and cost-effectiveness is not well defined. Although PET scan is a useful tool in assessing response to treatment, its routine use for follow-up is not recommended. Long-term sequelae of treatment include secondary malignancy, cardiovascular disease, pneumonitis, reproductive dysfunction, and hypothyroidism. Follow-up strategies for these sequelae need to be individualized, as their risks in general depend on the dose and volume of radiation to these organs, chemotherapy, age at treatment, and predisposing factors for each sequela. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Hodgkin lymphoma has gone from an incurable disease to one for which the majority of patients will be cured. Combined chemotherapy and radiotherapy achieves the best disease control rates and results in many long-term survivors. As a result, a majority of long-term Hodgkin lymphoma survivors live to experience severe late treatment-related complications, especially cardiovascular disease and second malignancies. The focus of research and treatment for Hodgkin lymphoma is to maintain the current high rates of disease control while reducing treatment-related morbidity and mortality. Efforts to reduce late treatment complications focus on improvements in both systemic therapies and radiotherapy. Herein we review the basis for the benefits of proton therapy over conventional X-ray therapy. We review outcomes of Hodgkin lymphoma treated with proton therapy, and discuss the ability of protons to reduce radiation dose to organs at risk and the impact on the most significant late complications related to the treatment.

The present guidelines review epidemiology, pathology, presentation, workup, staging, prognostic factors, and treatment options for patients with localized nodal indolent lymphoma, with an emphasis on radiation guidelines, including radiation dose, field design, and radiation techniques. Following a discussion of the current literature and available data for treatment and outcomes of patients with indolent lymphoma, several different example cases are reviewed to help physicians make appropriate treatment decisions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) by which the panel rates the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Pediatric Hodgkin lymphoma is a highly curable malignancy and potential long-term effects of therapy need to be considered in optimizing clinical care. An expert panel was convened to reach consensus on the most appropriate approach to evaluation and treatment of pediatric Hodgkin lymphoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four clinical variants were developed to assess common clinical scenarios and render recommendations for evaluation and treatment approaches to pediatric Hodgkin lymphoma. We provide a summary of the literature as well as numerical ratings with commentary. By combining available data in published literature and expert medical opinion, we present a consensus to the approach for management of pediatric Hodgkin lymphoma.

Approximately 70,130 cases of non-Hodgkin lymphoma are diagnosed annually in the United States and roughly 10 % occur in the skin. The cutaneous lymphomas are subclassified as primary cutaneous B-cell lymphoma or primary cutaneous T-cell lymphoma (PCTCL), and each subclassification includes a heterogenous group of diseases with different histologies, biologic markers, natural histories, and treatment responses. Mycosis fungoides (MF), a PCTCL, is the most common, making up 50 % of all cutaneous lymphomas. MF has unique systems for diagnosis, staging, and treatment based on clinical trials. Other primary cutaneous lymphomas are sufficiently rare to preclude clinical trials, so retrospective studies have informed treatment strategies. In general, these prospective and retrospective studies in cutaneous lymphomas suggest that skin-directed therapies, such as radiotherapy, surgery, and intralesional chemotherapy or steroids, are effective in indolent histologies, but systemic chemotherapy is the mainstay of therapy in more aggressive histologies. This chapter discusses the major types of primary cutaneous lymphoma and treatment strategies.

The optimal management of radiation proctitis is ill defined. A variety of alternatives are available and include topical agents (ie, sucralfate enemas, formalin), oral agents (ie, pentoxyfylline, vitamin A), hyperbaric oxygen, and endoscopic interventions (ie, argon plasma coagulation). It is prudent to manage patients conservatively and to intervene only when necessary with the option least likely to exacerbate the proctitis. Rectal biopsies should be avoided as they may precipitate a complication. More aggressive measures, such as argon laser coagulation, should be employed only when more conservative approaches fail.

Although a significant proportion of patients with localized prostate cancer are cured after definitive radiotherapy, solitary local recurrence is observed in a subset of patients and poses a management challenge. Curative-intent treatment options include prostatectomy, reirradiation, cryotherapy, and high-intensity-focused ultrasound. Outcomes data after any of these options are relatively limited. The 5-year biochemical progression-free survival rate is approximately 50% after salvage prostatectomy. However, the morbidity rate of the procedure is significantly higher compared with that observed in previously untreated patients. The likelihood of cure after low dose rate brachytherapy is similar to that observed after salvage prostatectomy, and the morbidity, although significant is less. Although cryotherapy and high-intensity-focused ultrasound may be less morbid than a prostatectomy, the probability of cure is probably lower.

To assess the potential benefit of proton therapy (PT) over photon therapy, we compared 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT plans in patients undergoing neoadjuvant chemoradiation for resectable rectal cancer at our institution.Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3DCRT, IMRT, and 3-dimensional conformal PT treatment planning. Initial target volumes (PTV1) were contoured using the Radiation Therapy Oncology Group anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2-cm expansion. Plans delivered 45 Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4-Gy (CGE) boost to the PTV2. Ninety-five percent of the PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal-tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient.All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. The proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to pelvic bone marrow at the V5Gy, V10Gy, V15Gy, and V20Gy levels and the small bowel space at the V10Gy and V20Gy levels. The proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the small bowel at the V30Gy and V40Gy levels and the urinary bladder at the V40Gy level.By reducing bone marrow exposure, PT may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who subsequently develop hematogenous metastasis. Reduced small bowel exposure using PT may also reduce toxicity and possibly facilitate the use of more-aggressive chemotherapy with radiotherapy.

The objective is to define the role of elective pelvic node irradiation (EPNI) in patients treated with definitive radiotherapy for clinically localized prostate cancer. Review of the pertinent literature revealed few prospective randomized trials that evaluated the efficacy of EPNI. Although EPNI may reduce the risk of regional recurrence, its impact on biochemical progression-free survival and overall survival is unclear. Depending on the extent of the radiotherapy fields, EPNI may result in a modest increase in acute toxicity and an even smaller increase in late toxicity. EPNI may reduce the risk of regional failure in patients with high-risk prostate cancer with a likelihood of lymph node positivity of ≥15%. Although it may result in improved biochemical progression-free survival, its impact is likely modest, at best. However, EPNI should be considered for patients with a high risk of regional disease.

The goal of the present study was to evaluate possible dosimetric advantages of proton therapy (PT) compared with 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in the treatment of patients with stage I and II seminoma.Two representative patients (1 with left-sided and 1 with right-sided seminoma) underwent treatment planning for stage I seminoma (paraaortic lymph nodes alone) with 3DCRT (PA3d), IMRT (PAimrt) double-scatter protons (PAPds), and uniform-scanning protons (PAPus) and for stage II seminoma (paraaortics lymph nodes and iliac nodes) with 3DCRT (PI3d) , IMRT (PIimrt) double-scatter protons (PIPds), and uniform-scanning protons (PIPus). The doses to the organs at risk were compared for photons and protons.For stage I seminoma, PT reduced the mean dose to the stomach, ipsilateral kidney, pancreas, bowel space, small bowel, and colon compared with 3DCRT and IMRT. For stage II seminoma, PT reduced the mean dose to the same organs as in stage I seminoma with additional reductions in mean dose to the bladder and rectum compared with 3DCRT and IMRT. Uniform-scanning protons further reduced the dose to the organs at risk compared with double-scatter protons.PT may offer an improvement in the therapeutic ratio in patients with seminoma by reducing the dose to normal tissue. This improvement may translate into lower risks of acute gastrointestinal side effects, infertility, and secondary malignancies, which should be explored in a prospective study.

Proton therapy can deliver a more conformal dose distribution than photon radiation and may allow safe dose escalation in stage III lung cancer. Early outcomes are presented here for patients who received proton therapy with concurrent chemotherapy for non-small-cell lung cancer (NSCLC).Nineteen patients with regionally advanced NSCLC were treated with concurrent chemotherapy (carboplatin and paclitaxel [n = 18]) and proton therapy from August 2008 to April 2010 either with (n = 7) or without (n = 12) induction chemotherapy. Eighteen patients had stage III NSCLC, and 1 patient had stage IIB disease. The median proton therapy dose was 74 cobalt gray equivalent (CGE) in 2 CGE fractions with 18 patients who received ≥70 CGE. Twelve patients also received selective nodal proton therapy to the adjacent uninvolved nodal regions, with a median dose of 40 CGE (range, 40-46 CGE). The patients were routinely evaluated for treatment-related toxicity and disease progression every 3 months, with a history, physical, and computed tomography or positron emission tomography-computed tomography.The median follow-ups for living patients were 15 and 16 months (range, 7-26 months), respectively. Nonhematologic and hematologic acute grade 3+ toxicity (90 days) developed in 1 and 4 patients, respectively. Two of 16 patients assessable for late toxicity (≥90 days) developed a significant grade 3+ nonhematologic late toxicity, whereas 1 patient developed a grade 3+ hematologic late toxicity. Local progression was the site of first relapse in one patient.Mediastinal proton therapy with concomitant chemotherapy was associated with acceptable toxicity. Although encouraging, longer follow-up with more patients is needed to confirm the long-term efficacy of this treatment.

Our objective was to determine if protons allow for the expansion of treatment volumes to cover high-risk nodes in patients with regionally advanced non-small-cell lung cancer. In this study, 5 consecutive patients underwent external-beam radiotherapy treatment planning. Four treatment plans were generated for each patient: 1) photons (x-rays) to treat positron emission tomography (PET)-positive gross disease only to 74 Gy (XG); 2) photons (x-rays) to treat high-risk nodes to 44 Gy and PET-positive gross disease to 74 Gy (XNG); 3) protons to treat PET-positive gross disease only to 74 cobalt gray equivalent (PG); and 4) protons to treat high-risk nodes to 44 CGE and PET-positive gross disease to 74 CGE (PNG). We defined high-risk nodes as mediastinal, hilar, and supraclavicular lymph nodal stations anatomically adjacent to the foci of PET-positive gross disease. Four-dimensional computed tomography was utilized for all patients to account for tumor motion. Standard normal-tissue constraints were utilized. Our results showed that proton plans for all patients were isoeffective with the corresponding photon (x-ray) plans in that they achieved the desired target doses while respecting normal-tissue constraints. In spite of the larger volumes covered, median volume of normal lung receiving 10 CGE or greater (V10Gy/CGE), median V20Gy/CGE, and mean lung dose were lower in the proton plans (PNG) targeting gross disease and nodes when compared with the photon (x-ray) plans (XG) treating gross disease alone. In conclusion, proton plans demonstrated the potential to safely include high-risk nodes without increasing the volume of normal lung irradiated when compared to photon (x-ray) plans, which only targeted gross disease.

RTOG 73-01 established standard doses of radiation for the treatment of patients with stage III non-small-cell lung cancer at 60 Gy in 2 Gy per fraction. However, overall survival was still poor, and local failures were a continuing problem. Over the next 30 years, a number of single institution and multi institution studies have been performed, attempting to improve overall survival by reducing local failures through radiation dose escalation either alone or in combination with chemotherapy with promising results. Additionally, new technology has been developed that can improve tumor imaging, deliver more conformal RT with less dose to normal structures, and decreased the set-up uncertainties, which has increased the therapeutic ratio and now allows for even safer dose escalation. The present chapter reviews these studies and discusses the current status of radiation dose escalation for patients with stage III NSCLC.

Introduction The purpose of this study was to determine the potential benefit of proton radiation therapy over photon radiation therapy in patients with unresectable stage III non-small-cell lung cancer. Materials and Methods Optimized 3-dimensional conformal photon (3DCRT), intensity-modulated radiation therapy (IMRT) and proton therapy (PT) plans were generated for 8 consecutive patients with unresectable stage III non–small-cell lung cancer using the same target goals and normal tissue constraints. The radiation exposure to non-targeted normal structures, including lung, bone marrow, esophagus, heart, and spinal cord, were compared. Photon doses are expressed in gray (Gy). Proton doses are expressed in cobalt gray equivalents (CGE). Results In all patients, 3DCRT, IMRT, and PT plans, achieved the dose goals for the target volumes. Compared with the 3DCRT plans, proton plans offered a median 29% reduction in normal lung V20 Gy (CGE), a median 33% reduction in mean lung dose (MLD), and a median 30% reduction in the volume of bone marrow receiving a dose of 10 Gy (CGE). Compared with the IMRT plans, the proton plans offered a median 26% reduction in normal lung V20 Gy (CGE), a median 31% reduction in MLD, and a median 27% reduction in the volume of bone marrow receiving a dose of 10 Gy (CGE). Conclusion By reducing the volumes of normal structures irradiated, protons can potentially improve the therapeutic index for patients with unresectable stage III non-small-cell lung cancer receiving combined radiation therapy and chemotherapy.

Purpose Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to the University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before ( n = 17) or after ( n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion ( p = .1935) and 369.9 ng/dL ( p = .1336), 348.7 ng/dL ( p = .7317), 353.4 ng/dL ( p = .6996), and 340.9 ng/dL ( p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions Conformal proton therapy to the prostate, as delivered using the University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

To characterize the incidence and pattern of neural invasion (NI) in patients with cancers of the paranasal sinuses and anterior skull base.Retrospective study.A tertiary referral cancer center.The study included 208 patients with cancer of the paranasal sinuses. Patients with brain invasion or neurogenic tumors were excluded.Analysis of clinical and pathologic data on patients with cancer of the paranasal sinuses.Forty-one specimens (20%) had evidence of NI. Sinonasal undifferentiated, adenoid cystic, and squamous cell carcinoma had a high propensity for NI, whereas melanoma and sarcoma rarely invaded nerves. Intraneural invasion was found in 32% of these cases, and 34% invaded more than 1 cm distal to the tumor. Neural invasion was associated with a high rate of positive margins, maxillary origin, and previous surgical treatment (P.04) but not with stage, orbital invasion, or dural invasion. Patients with NI were more likely to undergo adjuvant radiotherapy (P = .003), which significantly improved survival in patients with minor salivary gland carcinomas (P = .04). Multivariate analysis showed that pathologic evidence of NI was not an independent predictor of outcome.Paranasal carcinomas have high propensity for NI, whereas melanoma and sarcoma rarely invade nerves. Patterns of NI include both perineural and intraneural invasion. Neural invasion is associated with positive margins, maxillary origin, and previous surgery.

Purpose To analyze outcome, prognostic factors, and toxicities in patients with diffuse large-cell lymphoma (DLCL) who received involved-field radiotherapy (IFRT) before high-dose chemotherapy with autologous stem-cell rescue (ASCR). Patients and Methods Between January 1990 and August 2006, 164 patients with relapsed or refractory DLCL received IFRT at Memorial Sloan-Kettering Cancer Center (New York, NY) before high-dose chemotherapy and ASCR. IFRT was delivered to involved sites measuring more than 5 cm or to sites with residual disease more than 2 cm. Radiotherapy was administered in 1.5-Gy fractions twice daily to a total dose of 30 Gy. Progression-free survival and overall survival were calculated, and short- and long-term toxicity was assessed according to National Cancer Institute Common Toxicity Criteria (version 2.0). Median follow-up was 60 months (range, 2 to 187 months). Results Two- and 5-year progression-free survival was 62% and 53%; 2- and 5-year overall survival was 67% and 58%, respectively. Sixty-seven patients relapsed; only 10 patients relapsed completely within the radiotherapy field. There were seven early treatment-related mortalities and 11 secondary cancers (including four myelodysplastic syndromes), one of which occurred within the IFRT site and five after total-body irradiation. Conclusion Minimal treatment-related mortality and morbidity resulted from short, intensive, involved-field radiotherapy before high-dose chemotherapy and ASCR, which was incorporated into a salvage regimen for patients with relapsed/refractory DLCL. This chemoradiotherapy salvage regimen resulted in a low local relapse rate that could potentially translate into an improved total outcome.

Purpose To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy. Methods and Materials Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy ( n = 35, 90%) or with radiotherapy alone ( n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy ( n = 18, 46%), intensity-modulated radiotherapy ( n = 12, 31%), or conventional radiotherapy ( n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy ( n = 32, 82%) and/or concomitant boost radiotherapy ( n = 29, 74%). Results With a median follow-up of 90 months, the 5-year local progression–free survival, regional progression–free survival, distant metastasis–free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse ( n = 25, 64%), mostly within the irradiated field ( n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression–free survival and overall survival was a biologically equivalent dose of radiation ≥65 Gy. Conclusions Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control.

108 Background: Patients with intermediate risk prostate cancer choosing radiotherapy may be treated with a number of regimens. The current study compares the direct treatment cost for five therapeutic options based on Fiscal Year 2014 Medicare allowable reimbursements. Methods: Hypothetical charge sheets were generated along with the expected Medicare allowable reimbursements (based on global billing where applicable) for the following regimens: 1.) Image Guided Intensity Modulated Radiotherapy (IGIMRT) to a dose of 78Gy in 39 fractions with one field reduction (IGIMRT); 2.) Dose escalated IGIMRT to 84.60Gy in 47 fractions with one field reduction (MSKCC-IGIMRT); 3.)IGIMRT to a dose of 45Gy in 25 fractions followed by a 90 seed I125 prostate implant (IGIMRT-BTX); 4.) Image Guided Proton Therapy to a dose of 78Gy(RBE) in 39 fractions with one field reduction (SFPT); 5.) Image Guided Hypofractionated Proton Therapy to a dose of 72.50Gy(RBE) in 29 fractions with one field reduction (HFPT). Results: Based on Fiscal Year 2014 Medicare allowable reimbursements, the direct cost for each of these interventions including professional fees, technical fees, isotope costs and facility fees is shown in the Table. Conclusions: This data presents a framework for evaluating the cost effectiveness of proton therapy as compared to competing therapeutic options. Under current Medicare allowable reimbursements, the cost of proton therapy relative to the cost of other therapeutic options is highly dependent on the number of radiotherapy fractions delivered. The feasibility of delivering hypofractionated proton therapy for patients with localized prostate cancer is being investigated at a number of institutions as well as within the framework of a multicenter protocol. Ultimately the cost of proton therapy will need to be weighed against tumor control probabilities as well as the economic and quality of life benefits associated with reduced normal tissue exposure. [Table: see text]

Purpose: To perform a retrospective analysis of patients with paranasal sinus (PNS) cancer treated with postoperative radiotherapy (RT) at Memorial Sloan-Kettering Cancer Center. Methods and Materials: Between January 1987 and July 2005, 85 patients with PNS and nasal cavity cancer underwent postoperative RT. Most patients had squamous cell carcinoma (49%; n = 42), T4 tumors (52%; n = 36), and the maxillary sinus (53%; n = 45) as the primary disease site. The median radiation dose was 63 Gy. Of the 85 patients, 76 underwent CT simulation and 53 were treated with either three-dimensional conformal RT (27%; n = 23) or intensity-modulated RT (35%; n = 30). Acute and late toxicities were scored according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Results: With a median follow-up for surviving patients of 60 months, the 5-year estimates of local progression-free, regional progression-free, distant metastasis-free, disease-free, and overall survival rates were 62%, 87%, 82%, 55%, and 67%, respectively. On multivariate analysis, squamous cell histology and cribriform plate involvement predicted for an increased likelihood of local recurrence, and squamous cell histologic features predicted for worse overall survival. None of the patients who underwent CT simulation and were treated with modern techniques developed a Grade 3-4 late complication of the eye. Conclusion: Complete surgical resection followed by adjuvant RT is an effective and safe approach in the treatment of PNS cancer. Emerging tools, such as three-dimensional conformal treatment and, in particular, intensity-modulated RT for PNS tumors, may minimize the occurrence of late complications associated with conventional RT techniques. Local recurrence remains a significant problem.

The Value of Dose Constraints in Minimizing Rectal Toxicity in Patients Receiving Radiation Therapy for Prostate Cancer: Threeyear Analysis of Toxicity Outcomes in 2 Prospective Trials of Image Guided Proton Therapy for Earlyand Intermediate-Risk Prostate Cancer N.P. Mendenhall, Z. Li, B.S. Hoppe, R.B. Marcus, W.M. Mendenhall, R.C. Nichols, C.G. Morris, C.R. Williams, J. Costa, and R. Henderson; University of Florida Proton Therapy Institute, Jacksonville, FL, Division of Urology, College of Medicine, University of Florida, Jacksonville, FL