Cobalt Gray Equivalent Research Articles

80 INVITED Particle therapy: Physical potential amid clinical realities

To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients.Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10–20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3–46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2–68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy.Median follow-up time was 36 months (range, 8−77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency).Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.

Is Proton Beam Therapy Cost Effective in the Treatment of Adenocarcinoma of the Prostate?

New treatments are introduced routinely into clinical practice without rigorous economic analysis. The specific aim of this study was to examine the cost effectiveness of proton beam radiation compared with current state-of-the art therapy in the treatment of patients with prostate cancer. A Markov model was informed with cost, freedom from biochemical failure (FFBF), and utility data obtained from the literature and from patient interviews to compare the cost effectiveness of 91.8 cobalt gray equivalent (CGE) delivered with proton beam versus 81 CGE delivered with intensity-modulated radiation therapy (IMRT). The length of how many years the model was run, patient's age, probability of FFBF after treatment with proton beam therapy and IMRT, utility of patients treated with salvage hormone therapy, and treatment cost were tested in sensitivity analyses. Analysis at 15 years resulted in an expected mean cost of proton beam therapy and IMRT of $63,511 and $36,808, and $64,989 and $39,355 for a 70-year-old and 60-year-old man respectively, with quality-adjusted survival of 8.54 and 8.12 and 9.91 and 9.45 quality-adjusted life-years (QALY), respectively. The incremental cost effectiveness ratio was calculated to be $63,578/QALY for a 70-year-old man and $55,726/QALY for a 60-year-old man. Even when based on the unproven assumption that protons will permit a 10-Gy escalation of prostate dose compared with IMRT photons, proton beam therapy is not cost effective for most patients with prostate cancer using the commonly accepted standard of $50,000/QALY. Consideration should be given to limiting the number of proton facilities to allow comprehensive evaluation of this modality.

Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (< or =20% prescribed dose for both kidneys and < or =60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation.

Radiotherapy Treatment of Early-Stage Prostate Cancer with IMRT and Protons: A Treatment Planning Comparison

To compare intensity-modulated photon radiotherapy (IMRT) with three-dimensional conformal proton therapy (3D-CPT) for early-stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT). Ten patients were planned with both 3D-CPT (two parallel-opposed lateral fields) and IMRT (seven equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, [CGE] for protons) to the prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with nonstandard beam configuration, and for IMPT assuming delivery with beam scanning. At least 98% of the planning target volume received the prescription dose. IMRT plans yielded better dose conformity to the target, whereas proton plans achieved higher dose homogeneity and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving more than 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, whereas rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was reduced by up to 35% compared with the standard lateral configuration, whereas the bladder V70 increased by less than 10%. In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range lower than 50% of the target prescription was substantially lower with proton therapy.

Physiologic and Radiographic Evidence of the Distal Edge of the Proton Beam in Craniospinal Irradiation

Fatty replacement of bone marrow resulting from radiation therapy can be seen on T1-weighted magnetic resonance (MR) images. We evaluated the radiographic appearance of the vertebral bodies in children treated with proton craniospinal irradiation (CSI) to illustrate the distal edge effect of proton radiotherapy. The study cohort consisted of 13 adolescents aged 12-18 years who received CSI with proton radiotherapy at Massachusetts General Hospital. Ten of these patients had reached maximal or near-maximal growth. Proton beam radiation for these 10 patients was delivered to the thecal sac and exiting nerve roots only, whereas the remaining 3 patients had a target volume that included the thecal sac, exiting nerve roots, and entire vertebral bodies. Median CSI dose was 27 [range, 23.4-36] cobalt gray equivalent (CGE) given in 1.8-CGE fractions. Magnetic resonance images of the spine were obtained after completion of radiotherapy. Magnetic resonance images of patients who received proton radiotherapy to the thecal sac only demonstrate a sharp demarcation of hyperintense T1-weighted signal in the posterior aspects of the vertebral bodies, consistent with radiation-associated fatty marrow replacement. Magnetic resonance images of the patients prescribed proton radiotherapy to the entire vertebral column had corresponding hyperintense T1-weighted signal involving the entire vertebral bodies. The sharp delineation of radiation-associated fatty marrow replacement in the vertebral bodies demonstrates the rapid decrease in energy at the edge of the proton beam. This provides evidence for a sharp fall-off in radiation dose and supports the premise that proton radiotherapy spares normal tissues unnecessary irradiation.

Proton-Beam Therapy for Olfactory Neuroblastoma

To analyze the feasibility and efficacy of proton-beam therapy (PBT) for olfactory neuroblastoma (ONB) as a definitive treatment, by reviewing our preliminary experience. Olfactory neuroblastoma is a rare disease, and a standard treatment strategy has not been established. Radiation therapy for ONB is challenging because of the proximity of ONBs to critical organs. Proton-beam therapy can provide better dose distribution compared with X-ray irradiation because of its physical characteristics, and is deemed to be a feasible treatment modality. A retrospective review was performed on 14 patients who underwent PBT for ONB as definitive treatment at the National Cancer Center Hospital East (Kashiwa, Chiba, Japan) from November 1999 to February 2005. A total dose of PBT was 65 cobalt Gray equivalents (Gy(E)), with 2.5-Gy(E) once-daily fractionations. The median follow-up period for surviving patients was 40 months. One patient died from disseminated disease. There were two persistent diseases, one of which was successfully salvaged with surgery. The 5-year overall survival rate was 93%, the 5-year local progression-free survival rate was 84%, and the 5-year relapse-free survival rate was 71%. Liquorrhea was observed in one patient with Kadish's stage C disease (widely destroying the skull base). Most patients experienced Grade 1 to 2 dermatitis in the acute phase. No other adverse events of Grade 3 or greater were observed according to the RTOG/EORTC acute and late morbidity scoring system. Our preliminary results of PBT for ONB achieved excellent local control and survival outcomes without serious adverse effects. Proton-beam therapy is considered a safe and effective modality that warrants further study.

A Technique of Partial Breast Irradiation Utilizing Proton Beam Radiotherapy: Comparison with Conformal X-Ray Therapy

To develop a breast immobilization system and clinical technique to deliver partial breast irradiation with a proton beam and compare dose distributions using proton therapy and conformal x-rays. A clinical technique to provide reproducible breast immobilization was developed. Breast immobilization begins by fitting each patient with a treatment brassiere. Patients are placed prone in a cylindrical polyvinyl chloride shell with the upper and lower body being supported and immobilized with Vac-Lok foam bead cushions. The upper chest and breast areas are immobilized with two-part expandable foam. After a treatment planning computed tomography scan, the lumpectomy cavity is outlined, and a clinical target volume is generated by adding 1cm in all dimensions. A three-dimensional treatment plan is developed with treatment typically given with 2 to 4 separate proton beams. The dose administered is 40 cobalt Gray equivalents (CGE) delivered in 10 daily fractions of 4 CGE with multiple fields treated each day. Proton and conformal x-ray plans were compared using dose-volume histogram analysis to determine volumes of normal breast tissue and skin treated with each technique. An institutional review board-approved clinical trial was developed using this technique, and 20 patients have completed treatment. All subjects were able to undergo the immobilization procedure and daily treatments without significant discomfort, and no treatment interruptions were encountered. There was no evidence of respiratory motion identified on treatment planning CT images or on daily set-up radiographs. Acute toxicity has been limited to occasional radiation dermatitis (Radiation Therapy Oncology Group grade 1-2). Proton plans were compared with 2 methods of photon partial breast irradiation, including reduced tangential fields and five-field conformal techniques. Ten treatment plans with dose-volume histogram analysis revealed that the use of proton beams provided a significant reduction in doses to the ipsilateral breast and skin while eliminating doses to the heart and lung tissues. A simple immobilization procedure provides accurate and reproducible breast positioning while simultaneously eliminating respiratory motion. The procedure has been well tolerated by the first 20 patients. Protons can provide substantial normal tissue protection compared with the use of conformal x-rays when used for partial breast treatment. We plan to continue enrollment and analyze long-term toxicity, local control, and survival.

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.

Proton Beam Radiation Therapy for Skull Base Adenoid Cystic Carcinoma

To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. Retrospective analysis. Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. Locoregional control and disease-free survival and overall survival rates. Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P = .02) and involvement of sphenoid sinus and clivus (P = .01). High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors.

Protonentherapie mit „Spot-Scanning“ bei Rhabdomyosarkomen im frühen Kindesalter

To evaluate the feasibility and acute toxicity of spot-scanning proton therapy under deep sedation in young children with rhabdomyosarcomas (RMS).Since 2004, children requiring sedation can be admitted for proton therapy at Paul Scherrer Institute (PSI), Villigen, Switzerland. Children under 5 years of age with RMS of the head and the trunk were analyzed. All children were enrolled in a multidisciplinary treatment protocol and prospective, standardized evaluation of side effects was performed.Nine children were included aged 0.9-3.8 years (embryonal RMS in six, and alveolar, undifferentiated or nonclassified in one each). The tumor site was parameningeal (n = 4), orbital (n = 3), head and neck (n = 1), and prostate (n = 1). All children were in IRS group III. Total proton dose was 46-54 CGE (cobalt-gray equivalent). Only the myelotoxicity exceeded grade 3 or 4 (RTOG/EORTC).Proton therapy for RMS in early children is feasible and well tolerated. The prospective standardized evaluation of toxicity and quality of life needs to be continued.

Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison

The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration of vision were the indications for therapy. Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.

Accelerated partial breast irradiation using proton beams: Initial dosimetric experience

The unique dosimetric features of proton radiotherapy make it an attractive modality for normal tissue sparing. We present our initial experience with protons for three-dimensional, conformal, external-beam accelerated partial breast irradiation (3D-CPBI). From March 2004 to June 2005, 25 patients with tumors < or =2 cm and negative axillary nodes were treated with proton 3D-CPBI. The prescribed dose was 32 Cobalt Gray Equivalents (CGE) in 4 CGE fractions given twice daily. One to three fields were used to provide adequate planning target volume (PTV) coverage and dose homogeneity. Excellent PTV coverage and dose homogeneity were obtained in all patients with one to three proton beams. The median PTV receiving 95% of the prescribed dose was 100%. Dose inhomogeneity exceeded 10% in only 1 patient (4%). The median volume of nontarget breast tissue receiving 50% of the prescribed dose was 23%. Median volumes of ipsilateral lung receiving 20 CGE, 10 CGE, and 5 CGE were 0%, 1%, and 2%, respectively. The contralateral lung and heart received essentially no radiation dose. Cost analysis suggests that proton 3D-CPBI is only modestly more expensive (25%) than traditional whole-breast irradiation (WBI). Proton 3D-CPBI is technically feasible, providing both excellent PTV coverage and normal tissue sparing. It markedly reduces the volume of nontarget breast tissue irradiated compared with photon-based 3D-CPBI, addressing a principle disadvantage of external-beam approaches to PBI. As proton therapy becomes more widely available, it may prove an attractive tool for 3D-CPBI.

Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non–small-cell lung cancer

To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n=10) and 60-63 Gy, and 74 Gy in Stage III (n=15). For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p=0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p=0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT.

Proton beam radiotherapy for uveal melanoma: Results of Curie Institut–Orsay Proton Therapy Center (ICPO)

This study reports the results of proton beam radiotherapy based on a retrospective series of patients treated for uveal melanoma at the Orsay Center. Between September 1991 and September 2001, 1,406 patients with uveal melanoma were treated by proton beam radiotherapy. A total dose of 60 cobalt Gray equivalent (CGE) was delivered in 4 fractions on 4 days. Survival rates were determined using Kaplan-Meier estimates. Prognostic factors were determined by multivariate analysis using the Cox model. The median follow-up was 73 months (range, 24-142 months). The 5-year overall survival and metastasis-free survival rates were 79% and 80.6%, respectively. The 5-year local control rate was 96%. The 5-year enucleation for complications rate was 7.7%. Independent prognostic factors for overall survival were age (p < 0.0001), gender (p < 0.0003), tumor site (p < 0.0001), tumor thickness (p = 0.02), tumor diameter (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.003). Independent prognostic factors for metastasis-free survival were age (p = 0.0042), retinal detachment (p = 0.01), tumor site (p < 0.0001), tumor volume (p < 0.0001), local recurrence (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.002). Independent prognostic factors for local control were tumor diameter (p = 0.003) and macular area receiving at least 30 CGE (p = 0.01). Independent prognostic factors for enucleation for complications were tumor thickness (p < 0.0001) and lens volume receiving at least 30 CGE (p = 0.0002). This retrospective study confirms that proton beam radiotherapy ensures an excellent local control rate. Further clinical studies are required to decrease the incidence of postirradiation ocular complications.

Innovative Strategies for Image-Guided Proton Treatment of Prostate Cancer

Proton beam therapy has a proven track record of treating non-metastatic prostate cancer with excellent disease-free survival results when using homogeneous doses between 75 and 82 CGE (Cobalt Gray Equivalent) to the prostate target volume. In clinically organ-confined prostate cancer, it may be possible, in principle, to further improve outcomes by reducing the margins of the high-dose planning target volume to the gross tumor volume and by covering the clinical target volume with a dose sufficient to control microscopic extensions of the tumor. This would allow further dose escalation without increasing the risk of acute and late effects. In this paper, we undertake a careful review of existing histopathological data that support this view and discuss technical possibilities to this approach utilizing the highly conformal characteristics of proton beams and combining them with modern 4D imaging and treatment techniques.

Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma

To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence.

Résultats du traitement du mélanome malin de l’uvée par faisceau de protons : 10 ans de recul

We analyzed the long-term results of uveal melanoma treatment with proton beam irradiation in a series of patients with a follow-up of at least 10 years. The patients were treated with proton beam radiation between September 1991 and December 1992. They had an initial examination including visual acuity, funduscopy, A and B scan ultrasonography of the eye, fundus photographs and fluorescein angiography. General examination included chest radiography and B scan ultrasonography of the liver. All tumors received a total dose of 60 cobalt-Gray equivalents (applied in four daily fractions) at the Orsay proton therapy center. A total of 167 patients were treated with a median follow-up of 116 months. Their median age was 59 years. Thirteen tumors were anterior to the equator, 76 overlapped the equator and 78 were posterior to the equator. An initial retinal detachment was present in 41 cases. The optic disk was invaded in 10 cases. The median tumor diameter was 12 mm and the median tumor thickness was 5.8 mm. The mean initial acuity was 20/50. The survival rate was 62.93% at 10 years; 72.9% of deaths resulted from metastasis. Statistically significant risk factors for death identified in the multivariate analysis were tumor diameter greater than 12 mm (p=0.0004) and age over 60 years (p=0.0001). The metastasis rate at 10 years was 31%. The liver was affected in 97.8% of these patients. Risk factors for metastasis were the anterior site of the tumor, its volume greater than 0.4 cc and the presence of retinal detachment at diagnosis. The secondary enucleation rate at 10 years was 13.23%, mainly attributable to secondary neovascular glaucoma. The local recurrence rate was 6%. The visual acuity rate in 42.1% of patients was better than 20/100 at 10 years. Visual loss was mainly due to postradiation maculopathy and neuropathy. Our study confirms the long-term results found in the literature on proton beam radiation. This therapy allows good tumor control, an excellent eye retention rate, and good final visual acuity for approximately half of the patients.

Patterns of Neck Relapse After Elective Nodal Irradiation for Sinonasal Tumors: Implications for Nodal Volume Delineation

Materials/Methods: Between 1991 and 2002, 100 consecutive patients with newly diagnosed sinonasal malignancies received combined proton and photon radiotherapy (RT) at the Massachusetts General Hospital. There were 33 squamous cell carcinomas (SCC), 28 neuroendocrine tumors, 20 adenoid cystic carcinomas (ACC), 14 soft tissue sarcomas (STS), and 5 adenocarcinomas. One patient had T1, 7 with T2, 18 with T3 and 74 with T4 primary tumors according to the 2002 AJCC staging system. Ninety-seven and 3 patients presented with N0 and N1 neck respectively. The median prescribed total RT dose to the primary was 71.1 Cobalt Gray Equivalent (CGE) (range: 55.4 77.8). The neck RT treatments were: 67% bilateral ENI, 11% unilateral ENI, and 22% no ENI. ENI was delivered by 4 MV photons to a median dose of 44Gy (range: 37.5 60) over 23 fractions. The majority of neck portals were delivered using an AP/PA approach with a full midline cord and chin block to encompass the cervical and supraclavicular nodes. The neck fields were matched to the inferior border of the proton fields encompassing the primary tumor at the level of C1-3, the retropharyngeal nodes were not fully encompassed in the radiation portals in most cases. Thirty-four percent of patients received chemotherapy, 68% of patients underwent surgical resection of the primary prior to RT.

Cauda equina tolerance to high-dose fractionated irradiation

To report late neurologic toxicity rates and clinical outcomes for patients treated with high dose fractionated radiation therapy using three-dimensional treatment planning and combined proton and photon beams to portions of the cauda equina (L2-coccyx). Medical records of 53 patients treated to fields encompassing the cauda equina were reviewed for the onset of neurologic symptoms in the absence of local failure. All doses were normalized to equivalent dose delivered in 2-Gy fractions. Median cauda dose was 65.8 cobalt Gray equivalents (CGE) (range, 31.9-85.1). Median follow-up was 87 months (range, 14-217 months). Nineteen patients experienced local recurrences, and 13 others had neurologic toxicity. A total of 54% (i.e., 7/13) of the toxicities occurred 5 years or more after treatment. Median caudal dose was 73.7 CGE in the group with neurologic toxicity, and 55.6 CGE in those without. On multivariate actuarial analysis, cauda dose and gender were statistically significant for neurotoxicity at p = 0.002 and p = 0.017, respectively. The estimated tolerance doses 5 years from treatment, TD 5/5 and TD 50/5, were 55 CGE and 72 CGE, respectively, for males and 67 CGE and 84 CGE for females. The tolerance doses were about 8 CGE lower when estimated at 10 years from treatment. Disease-free survival rates at 5 and 10 years were 66% and 53%, respectively. This study suggests that the probability of neurotoxicity is a relatively steep function of dose to cauda equina (slope gamma50 = approximately 3). The cauda equina tolerance is greater for females than males by about 11 CGE (at 2 CGE per fraction). Extended follow-up is necessary to accurately assess neurologic damage and then differentiate that phenomenon from local recurrence; the traditional 5-year assessment has limited meaning in this population. Local control remains an issue for these patients, even with the radical doses used.

Les chordomes de la base du crâne et du rachis cervical haut. À propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons

To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine.Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively.With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival.In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.