Cobalt Gray Equivalent Research Articles

Radiation-induced malignant meningioma following proton beam therapy for a choroidal melanoma

We report a woman with malignant meningioma diagnosed 9years after the treatment of a choroidal melanoma with proton beam therapy. The risk of secondary cancers is a well-known adverse late effect of radiation therapy, especially with the use of advanced techniques such as intensity-modulated radiation therapy. However, this risk may be less with the use of proton beam therapy. A 79-year-old woman presented with symptoms of enophthalmos, ptosis and paralysis of the left medial rectus muscle. She had previously been successfully treated for a choroidal melanoma of the left eye with proton beam therapy (total dose: 60 cobalt gray equivalents) following local resection. MRI showed a lesion in the left cavernous sinus with extension into the orbit and a subsequent biopsy revealed a papillary meningioma. The cavernous tumor was treated with photon radiotherapy (total dose: 54Gy) which achieved an initial partial response. However, 8months later the tumor extensively metastasized to the skull and the spine and the patient died 1year after the treatment. The incidence of secondary malignancies after proton beam therapy is low but not negligible, therefore, it must be taken into account when planning a treatment as secondary tumors may present with a highly aggressive behaviour.

Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non–Small-Cell Lung Cancer: A Dosimetric Study

BackgroundPhoton involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Patients and MethodsIMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. ResultsProton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). ConclusionThis study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT.

Long-Term Outcomes After Proton Beam Radiation Therapy for Intraocular Vascular Tumors

Purpose/Objective(s): To present long-term follow-up for patients with intraocular vascular tumors treated with proton beam radiation therapy (PBRT). Materials/Methods: We performed a review of our prospectively maintained database for all patients with intraocular vascular tumors treated with PBRT at our institution between 1994 and 2012. We report patient demographics, tumor characteristics, dose schemes, treatment responses, and complications. Patients with at least 6 months of follow-up data were included in the study. Results: Our review identified 29 evaluable patients (29 eyes) with vascular tumors of the eye, with the most common diagnosis being choroidal hemangioma (n Z 22). Additionally, three diffuse choroidal hemangiomas associated with Sturge-Weber syndrome, three retinal angiomas, and one hemangioblastoma associated with von Hippel-Lindau syndrome were also identified. The main analysis hereafter focuses on the choroidal hemangioma patients (n Z 22), with mean follow-up time of 78.5 months (range 12-177 months, median 69.2 months). Median age at diagnosis was 48.3 years (range 17-72). All 22 patients were symptomatic at the time of diagnosis. Initial tumor thickness, as measured by ultrasonography, ranged from 2.0 mm to 7.2 mm (mean 3.8 mm). All patients except one had the anterior tumor border located posterior to the equator. Patients were treated using total doses between 18 and 24 Cobalt Gray Equivalent (CGE) in four fractions. Best corrected visual acuity improved or remained stable in 20 of 22 eyes (91%). Of the 16 eyes initially presenting with retinal detachment, 15 experienced reattachment (94%). Cystoid macular edema was initially documented in 16 eyes and completely resolved in 13 eyes (81%). Subretinal fluid was initially present in 17 eyes and resolved in 16 eyes (94%). Tumor thickness decreased in all eyes as of last examination. Notable complications occurred in five patients, with the most common being radiation retinopathy and atrophy; anti-VEGF therapy was used for treatment. Nine patients received full dose to the disc and macula (range 18-24 CGE), none of whom had significant worsening of vision. The additional seven intraocular vascular tumors with variable histologies have also demonstrated tumor response after PBRT at mean follow-up of 29.5 months (median 24.4 months) with stable or improved visual acuity. Conclusions: This series demonstrates consistent and long-term tumor response and visual preservation in patients with benign vascular tumors of the eye, including choroidal hemangiomas, diffuse hemangiomas with Sturge-Weber syndrome, retinal angiomas, and hemangioblastoma related to von Hippel-Lindau syndrome. The data presented represents the longest available follow-up in the literature to date for choroidal hemangiomas treated with PBRT. Author Disclosure: E.M. Chang: None. D.H. Char: None. D. Jusufbegovic: None. I.K. Daftari: None. T.B. Cole: None. J.M. Quivey: None. T.L. Phillips: None. K.K. Mishra: None.

Proton Beam Therapy Leads to Excellent Local Control Rates in Choroidal Melanoma in the Intermediate Fundus Zone

To evaluate long-term outcomes of proton beam radiotherapy in the treatment of choroidal melanoma of the intermediate zone of the fundus. Retrospective interventional single-center study. The study was a retrospective analysis with long-term follow-up of 62 patients with a minimum tumor-to-disc and tumor-to-fovea distance of 2 mm of choroidal melanoma in the intermediate zone of the fundus. Mean values of tumor prominence, largest basal diameter, and tumor distances to the optic disc and fovea were 7.6, 12.8, 5.2, and 4.6 mm, respectively. All patients were irradiated with a total proton dose of 60 cobalt gray equivalents. After proton beam radiotherapy, 71.0% of the patients received subsequent endoresection of the tumor. Only 18 patients (29.0%) did not require additional tumor resection and were analyzed as a separate group. For the total of patients, the median follow-up time was 70.3 months. The 5-year Kaplan-Meier rates of local tumor relapse, enucleation, and distant metastasis were 3.9%, 3.7%, and 13.4%, respectively. Cataract surgery was the most frequent secondary treatment in our cohort. In this study we demonstrate the effectiveness of proton beam irradiation in tumor control and preservation of the globe in the analyzed patients. The rate of metastasis was not higher than previously described. Nevertheless, consecutive tumor surgery is frequently required to maintain the eye in patients with large-sized choroidal melanomas. In conclusion, proton beam radiotherapy allows preservation of the eye in mid-zone choroidal melanomas.

Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases

To report the clinical features and outcomes of iris melanomas treated by proton beam therapy. A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon, Department of Ophthalmology, in 36 patients treated by proton beam therapy for presumed (n = 29) and confirmed (n = 7) iris melanomas between July 1997 and October 2010. Ciliary body melanomas with iris involvement were excluded. The patients' mean age was 54.4 years (range, 22-82 years). The average tumor diameter was 3.8 mm (range, 2.5-8.0). The iridocorneal angle was invaded by the tumor in 47% of cases (n = 17), the ciliary body in 17% of cases (n = 6), and the sclera in 3% (n = 1). Raised intraocular pressure was present before treatment in 11.1 % of cases (n = 4). Tumor biopsy was performed in 19% of cases (n = 7). Four patients had undergone an initial incomplete surgical excision of tumor before radiotherapy. Surgical preparation of the eye with tantalum ring positioning had been performed in all cases 3-4 weeks before irradiation. The prescribed dose was 60 Cobalt Gray Equivalent (CGE) of proton beam radiotherapy delivered in four fractions on four consecutive days. The median follow-up was 50 months (mean 60.5, range 15-136). One patient (2.7%) was lost to follow-up. None of the patients showed tumor progression, local recurrence, or metastasis. None of the patients required secondary enucleation. Cataract was developed in 62% of patients, glaucoma in two cases (6%) after irradiation, and hyphema with the aggravation of pre-existing glaucoma in one patient. No patients developed neovascular glaucoma. Proton beam therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable rate of complications. Longer follow-up studies on a larger series is necessary to consolidate these results.

SU‐E‐J‐143: Short‐ and Near‐Term Effects of Proton Therapy On Cerebral White Matter

Purpose:To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near‐term development of such effects.Methods:Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract‐based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone to high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated.Results:The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P&lt;0.05) decline of FA was observed 3 months after proton therapy in all VOIs except the PLIC and ranged from −1.7% (ALIC) to −2.8% (PCT). A significant increase of RD was found in the CP (3.5%) and ALIC (2.1%). The average longitudinal change from the baseline was reduced at 12 months for most VOIs. However, the standard deviation increased, indicating that the temporal pattern varied individually. The follow‐up measurements at 3 and 12 months correlated for the CP, CST, PCT, and GCC (P &lt; 0.04).Conclusion:DTI data suggest early (3 months) effects of proton therapy on microstructures in the white matter. The subsequent follow‐up indicated individual variation of the changes, which was partly implied by the early effects.

SU‐E‐J‐122: Detecting Treatment‐Induced Metabolic Abnormalities in Craniopharyngioma Patients Undergoing Surgery and Proton Therapy

Purpose:To identify treatment‐induced defects in the brain of children with craniopharyngioma receiving surgery and proton therapy using fluorodeoxyglucose positron emission tomography (FDG PET).Methods:Forty seven patients were enrolled on a clinical trial for craniopharyngioma with serial imaging and functional evaluations. Proton therapy was delivered using the double‐scattered beams with a prescribed dose of 54 Cobalt Gray Equivalent. FDG tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if exceeding two standard deviations of normal population from the mean. For establishing the normal ranges, 132 children aged 1–20 years with noncentral nervous system related diseases and normal‐appearing cerebral PET scans were analyzed. Age‐ and gender‐dependent regional uptake models were developed by linear regression and confidence intervals were calculated.Results:Most common PET abnormality before proton therapy was significantly low uptake in the frontal lobe, the occipital lobe (particularly in cuneus), the medial and ventral temporal lobe, cingulate gyrus, caudate nuclei, and thalamus. They were related to injury from surgical corridors, tumor mass effect, insertion of a ventricular catheter, and the placement of an Ommaya reservoir. Surprisingly a significantly high uptake was observed in temporal gyri and the parietal lobe. In 13 patients who already completed 18‐month PET scans, metabolic abnormalities improved in 11 patients from baseline. One patient had persistent abnormalities. Only one revealed new uptake abnormalities in thalamus, brainstem, cerebellum, and insula.Conclusion:Postoperative FDG PET of craniopharyngioma patients revealed metabolic abnormalities in specific regions of the brain. Proton therapy did not appear to exacerbate these surgery‐ and tumor‐induced defects. In patients with persistent and new abnormalities, continued investigation on clinical symptoms and cognitive outcomes is ongoing to establish the association and predictive values of metabolic imaging.

Proton beam irradiation for non-AMD CNV: 2-year results of a randomised clinical trial

AimsTo evaluate safety and visual outcomes after proton beam irradiation (PBI) therapy for subfoveal choroidal neovascularisation (CNV) secondary to causes other than age-related macular degeneration (AMD).MethodsThis study is a prospective,...

Long-term (4 years) results of choroidal hemangioma treated with proton beam irradiation.

The aim of this retrospective study was to determine the efficacy of proton beam irradiation in choroidal hemangioma in a long-term follow-up. A total dose of 20 Cobalt Gray equivalent (CGE) was administered to 50 eyes of 50 patients from September 1998 to September 2010. All treated patients presented with a symptomatic tumor. Nine patients were pre-treated by photodynamic therapy (PDT). Visual outcome, tumor regression, and complications resulting from radiation were investigated. The mean follow-up was 55.4 months (range 13-132). Tumor thickness decreased in all patients. Retinal re-attachment was achieved without evidence of tumor leakage. Visual acuity improved by two lines after one year in 43.4 % of patients and after two years in 36.8 % of patients. During the 55.4 months of long-term follow-up the visual acuity improved from 6/15 to 6/12 after proton therapy. Twenty-three patients (46.0 %) developed radiation retinopathy. According to the Finger classification of 2004, 21 patients (42.0 %) showed a stage 1 or 2 (functionally not relevant) retinopathy, and two patients (4.0 %) presented a stage 3 or 4 (functionally relevant) retinopathy. Further complications included sicca syndrome in nine cases, cataract formation in 10 cases, and radiation optic neuropathy in four cases. Proton therapy with 20 CGE is an efficient primary therapy in choroidal hemangioma and is very effective as a secondary treatment after PDT.

Proton Beam Therapy of Parapapillary Choroidal Melanoma

To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. Clinical case series, retrospective study. We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.

Five-Year Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes.

First report of a prospective trial of proton therapy and concomittant capecitabine for patients with nonmetastatic unresectable pancreatic adenocarcinoma.

326 Background: Review initial outcomes for patients enrolled on the University of Florida Proton Therapy Institute PC01 protocol for patients with unresectable pancreatic cancer. Methods: The protocol received Institutional Review Board (IRB) approval in 7/2007. The first patient was enrolled in 4/2010. The accrual target was 66 patients to test if the Serious Adverse Event (SAE) ratecould be reduced from 15% (expected) to less than 5%. Protocol therapy consisted of proton therapy to a planning target volume (PTV) dose of 59.4 Cobalt Gray Equivalent (CGE) at 1.8CGE per fraction with concomitant oral Capecitabine (1000mg PO BID 5 days/week on radiation treatment days). Only gross disease was targeted. Results: 12 patients were enrolled. 1 patient died of a gunshot wound 5 days after starting treatment so only 11 patients are reported. Median follow up from start of treatment: 13 months (range 2 to 21 months). Median age: 68 (range 51 to 86) years. Gender: Males 5, Females 6. Race/Ethnicity: 9 White, 2 Hispanic. Overall survival: 90% at 6 months and 60% at 12 months. Freedom from progression: 80% at 6 months and 53% at one year. Local control: 100% at 6 months and 86% at 12 months. Freedom from metastasis: 80% at 6 months and 67% at 12 months.No patient experienced any grade 3 or greater toxicity during treatment or the follow up period. Grade 2 toxicity was limited to a single patient experiencing grade 2 fatigue. Median weight loss over the course of treatment was 1.7 (range: loss of 5.7 to gain of 4.9) Kg. 4 patients were deemed to have had an adequate radiographic response to radiotherapy so as to justify surgical exploration. Conclusions: Proton therapy to 59.4 CGE with concomitant Capecitabine was well tolerated with no grade 2 or greater gastrointestinal toxicities. 4 of 11 patients achieved a radiographic response allowing for attempted surgical resection. The study was closed to accrual on 9/1/2013 due to recognition that slow accrual made achievement of the primary study endpoint unlikely. At the same time, the lack of any meaningful gastrointestinal toxicity suggests significant opportunities for treatment intensification when proton therapy is used in this setting. Clinical trial information: NCT00685763.

Dosimetric impact of number of treatment fields in uniform scanning proton therapy planning of lung cancer.

The main purpose of this study was to perform a treatment planning study for lung cancer comparing 2-field (2F) versus 3-field (3F) techniques in uniform scanning proton therapy (USPT). Ten clinically approved lung cancer treatment plans delivered using USPT at our proton center were included in this retrospective study. All 10 lung cases included 4D computed tomography (CT) simulation. The delineation of target volumes was done based on the maximum intensity projection (MIP) images. Both the 3F and 2F treatment plans were generated for the total dose of 74 cobalt-gray-equivalent (CGE) with a daily dose of 2 CGE. 3F plan was generated by adding an extra beam in the 2F plan. Various dosimetric parameters between 2F and 3F plans were evaluated. 3F plans produced better target coverage and conformality as well as lower mean dose to the lung, with absolute difference between 3F and 2F plans within 2%. In contrast, the addition of third beam led to increase of low-dose regions (V20 and V5) in the lung in 3F plans compared to the ones in 2F plans with absolute difference within 2%. Maximum dose to the spinal cord was lower in 2F plans. Mean dose to the heart and esophagus were comparable in both 3F and 2F plans. In conclusion, the 3F technique in USPT produced better target coverage and conformality, but increased the low-dose regions in the lung when compared to 2F technique.

Preliminary results of proton radiotherapy for choroidal melanoma - the Kraków experience.

Aim of the studyThe objective of the study was to present the preliminary results of proton radiotherapy as a method for treating 15 patients with choroidal melanoma.Material and methodsThe proton radiotherapy was administered using beams providing energy levels of 60 MeV, which ensures a clinical range of 28.4 mm. In addition, the beam has a very narrow penumbra of 1.3 mm and a sharp distal dose fall-off. All patients received the dose of 60 CGE (cobalt gray equivalent) given to the PTV (planning target volume). This dose was administered in 4 fractions over 4 successive days of treatment.ResultsThe tumour had regressed in 8 patients (53.3%) and remained stable in 3 patients (20%). The large tumours in another 3 patients (20%) were removed during vitrectomy (endoresection), which increased the number of patients with tumour regression up to 11 (73.3%). In the case of 1 patient, despite intraocular tumour regression occurring the choroidal melanoma had spread multifocally into the orbit, which necessitated orbit exenteration. The results ensured that the eyeballs of 14 patients (93.3%) could be saved.The follow-up period for the 15 patients ranged between 8 and 26 months (average: 17.4 months, median: 19 months). In this period some side effects were noted: an increase in intraocular pressure, retinal detachment, cataract, maculopathy, neuropathy and vitreous haemorrhaging.ConclusionsThe preliminary results confirm that proton radiotherapy is an effective method for treating patients with choroidal melanoma. This method ensures an eyeball preservation rate of 93%, with the vision function of 80% of the patients being saved.

RE: Takatori K, Terashima K, Yoshida R, Horai A, Satake S, Ose T, Kitajima N, Kinoshita Y, Demizu Y, Fuwa N. Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer. J Gastroenterol. 2013; (E-pub only).

To the editor, Dr. Takatori and colleagues deserve praise for meticulously studying the extent and severity of upper gastrointestinal (GI) complications in 91 inoperable pancreatic cancer patients treated on a prospective clinical trial with proton-based radiotherapy and concomitant gemcitabine chemotherapy (GPT) (1). The significant complications observed in this series (49.4% rate of gastric/duodenal ulceration), however, starkly contrast the favorable toxicity profile we observed in our series of pancreatic cancer patients treated with proton therapy and concomitant capecitabine chemotherapy (2). In our series, we observed no grade 3 toxicities in patients receiving proton doses ranging from 50.40 to 59.40 Cobalt Gray Equivalent (CGE) at 1.8 CGE per daily fraction with daily oral capecitabine (1,000 mg twice daily). The median weight loss during treatment was only 1.3 kg (1.75% of body weight). Additionally, when radiotherapy plans avoided the use of anterior or left lateral fields—reducing small bowel and gastric exposure—grade 2 GI toxicity was eliminated and median weight loss was only 0.5 kg. Possible explanations for the disparity of outcomes between these two series might include: (I) aggressive radiotherapy doses [67.5 Gray equivalent (GyE)] and high dose per fraction (2.7 GyE) delivered in the GPT series; (II) concomitant delivery of full-dose gemcitabine (800 mg/m2 on days 1, 8, and 15), well-recognized as a potent radiosensitizing agent; and (III) radiotherapy fields expanded to include regional lymph nodes in addition to the primary tumor. Although details of the radiotherapy plans were not included in the GPT publication, it is possible that some of the toxicity might have been mitigated if anterior and left lateral fields had been avoided or the dose delivered through such fields was minimized. While the current study is well-designed and well-reported, it would be wrong to conclude that proton therapy for patients with pancreatic cancer is associated with a high rate of gastrointestinal toxicity. Indeed, we have every reason to believe, based on its superior dosimetry (3), that proton therapy offers significant improvements in the therapeutic index compared to X-ray-based therapies such as intensity-modulated radiotherapy. Our clinical experience helps confirm the hypothesis, based on this dosimetry, that proton therapy reduces GI toxicity and may allow for treatment intensification—although perhaps not to the same degree as the intensification offered on the GPT protocol. We appreciate you taking the time to consider our letter and look forward to hearing from you in the future.

INTRAVITREAL DEXAMETHASONE 0.7-MG IMPLANT FOR RADIATION MACULAR EDEMA AFTER PROTON BEAM THERAPY FOR CHOROIDAL MELANOMA

To evaluate the efficacy of dexamethasone 0.7-mg intravitreal implant in patients with radiation macular edema after proton beam therapy for choroidal melanoma. Five patients' charts were retrospectively reviewed. The main outcome measures were visual acuity and mean central retinal thickness. All patients received a radiation dose of 60 cobalt gray equivalent. Radiation macular edema occurred within a mean time of 26 months after irradiation. Mean preinjection visual acuity was 41 Early Treatment Diabetic Retinopathy Study letters. Mean central retinal thickness was 487.1 μm. Two months after injection, mean visual acuity was 47 Early Treatment Diabetic Retinopathy Study letters. It improved for 3 patients (+4, +9 and, +15 letters) and remained unchanged for 2. Mean central retinal thickness was 331 μm. It decreased for 4 patients (-111, -134, -336, and -187 μm). Two patients underwent a second injection of dexamethasone performed 5 months after the first injection. The gain of visual acuity was +8 and +23 letters with a decrease in central retinal thickness of 158 and 262 μm, respectively. Intraocular pressure increased for 1 patient over a mean follow-up period of 6.4 months. Intravitreal dexamethasone implant can improve visual acuity in radiation macular edema. The observed beneficial effect lasted up to 5 months.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

Use of dexamethasone 0.7mg intravitreal implant in radiation macular edema

AbstractPurpose To evaluate the efficacy and safety over one year of follow‐up of dexamethasone 0.7mg intravitreal implant in patients with radiation macular edema (ME) after proton beam therapy for choroidal melanomaMethods Five patients’ charts were retrospectively reviewed.Results All patients received a radiation dose of 60 cobalt Gray equivalent. Radiation ME occurred within a mean time of 26 months after irradiation. Mean preinjection VA was 41 ETDRS letters. Two months after injection, mean VA was 47 ETDRS letters. It improved for 3 patients (+4; +9 and +15 letters) and remained unchanged for 2. Mean CRT was 331 µm. Over one year of follow‐up, two patients underwent 2 injections of dexamethasone performed 5 months after the first injection. The gain of VA was +8 and +23 letters with a decrease in CRT of 158 and 262 µm respectively. Intraocular pressure increased for 1 patient. One patient was enucleated due to a local recurrence of his choroidal melanoma. Another patient presented with a radiation neuropathy with a great loss of visual acuity.Conclusion Intravitreal dexamethasone implant can improve VA in radiation ME. Its beneficial effect lasted up to 5 months. Other causes of vision loss may jeopardize this beneficial effect.

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

Background and purposeHere, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS). Materials and methodsThirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days. ResultsAll patients completed PB-APBI. The median follow-up time was 59months (range: 43–70months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2months that was not observed beyond 6months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2months, respectively, and decreased to 69% at 3years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p=0.02); however, it did not increase in patients treated with two-field PB-APBI (p=0.3). ConclusionsPB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.

Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer.

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.