Conformal radiation therapy for childhood CNS tumors

Radiation therapy plays a central role in the management of many childhood brain tumors. By combining advances in brain tumor imaging with technology to plan and deliver radiation therapy, pediatric brain tumors can be treated with conformal radiation therapy. Through conformal radiation therapy, the radiation dose is targeted to the tumor, which can minimize the dose to normal brain structures. Therefore, by limiting the radiation dose to normal brain tissues, conformal radiation therapy offers the possibility of limiting the long-term side effects of brain irradiation.In this review, we describe different approaches to conformal radiation therapy for pediatric central nervous system tumors including: A) three-dimensional conformal radiation therapy; B) stereotactic radiation therapy with arc photons; C) intensity-modulated radiation therapy; and D) proton beam radiation therapy. We discuss the merits and limitations of these techniques and describe clinical scenarios in which conformal radiation therapy offers advantages over conventional radiation therapy for treating pediatric brain tumors.     

Intensity-modulated radiation therapy for malignancies of the nasal cavity and paranasal sinuses

PURPOSE: To report the clinical outcome of patients treated with intensity-modulated radiation therapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. METHODS AND MATERIALS: Between 1998 and 2004, 36 patients with malignancies of the sinonasal region were treated with IMRT. Thirty-two patients (89%) were treated in the postoperative setting after gross total resection. Treatment plans were designed to provide a dose of 70 Gy to 95% or more of the gross tumor volume (GTV) and 60 Gy to 95% or more of the clinical tumor volume (CTV) while sparing neighboring critical structures including the optic chiasm, optic nerves, eyes, and brainstem. The primary sites were: 13 ethmoid sinus, 10 maxillary sinus, 7 nasal cavity, and 6 other. Histology was: 12 squamous cell, 7 esthesioneuroblastoma, 5 adenoid cystic, 5 undifferentiated, 5 adenocarcinoma, and 2 other. Median follow-up was 51 months among surviving patients (range, 9-82 months). RESULTS: The 2-year and 5-year estimates of local control were 62% and 58%, respectively. One patient developed isolated distant metastasis, and none developed isolated regional failure. The 5-year rates of disease-free and overall survival were 55% and 45%, respectively. The incidence of ocular toxicity was minimal with no patients reporting decreased vision. Late complications included xerophthalmia (1 patient), lacrimal stenosis (1 patient), and cataract (1 patient). CONCLUSION: Although IMRT for malignancies of the sinonasal region does not appear to lead to significant improvements in disease control, the low incidence of complications is encouraging.     

Conformal radiotherapy for paranasal sinus and nasal cavity tumors: three-dimensional treatment planning and preliminary results in 40 patients

PURPOSE: To assess the possibility to deliver a high and homogeneous irradiation with respect to maximal tolerated dose to the visual pathways for paranasal sinus and nasal cavity tumors. METHODS AND MATERIALS: Forty patients with advanced stage malignant tumors were treated with postoperative (30) or primary (10 patients) conformal radiotherapy (CRT). Five patients were previously irradiated. Six to 15 individually shaped isocentric noncoplanar field arrangements, using a multileaf collimator were designed. Dose-volume histograms (DVH) for the planning target volumes (PTV) and the optic pathways were analyzed in 31 cases. RESULTS: Median and maximal delivered doses to the PTV were 60 (+/-3) and 66 (+/-4) Gy. Dose distributions for critical organs are detailed. Median follow-up was 19 months (3 to 48). Local, nodal, and metastatic recurrences occurred in 8, 2, and 7 cases, respectively. Major prognostic factor for local recurrences was central nervous system (CNS) involvement. One patient died of meningitis. Two patients developed cataract, and 1 patient ipsilateral blindness due to vascular glaucoma. CONCLUSION: CRT for locally advanced paranasal sinus and nasal cavity tumors enables the delivery of high homogeneous doses to the PTV with respect to critical organs, with a low toxicity and a high local control.     

Conformal three-dimensional photon radiotherapy for paranasal sinus tumors.

BACKGROUND: Tumors in the nasal cavity and paranasal sinus are difficult to treat with radiotherapy. Usually, in addition to a two- or three-field photon technique, an interorbital electron field is required. This may result, however, in severe over- or underdosage, the latter being especially detrimental when occurring in the main tumor bulk. METHODS AND RESULTS: We present a conformal three-dimensional treatment technique that provides sufficient interorbital dose with photons only while sparing the eyes, optic nerves and chiasm, and may be considered for selected tumors in this region.     

Endoscopic surgery with curative intent for malignant tumors of the nose and paranasal sinuses

Aim

To assess the efficacy of endoscopic surgical treatment in patients with nasal and paranasal sinus malignancies.

Patients and methods

During the period 1991–2006, 16 patients with nasal and paranasal sinus malignancies underwent endoscopic surgery with curative intent. The lesions included 11 carcinomas, two malignant melanomas, one olfactory neuroblastoma, one hondrosarcoma and one leiomyosarcoma. Tumors originated from the ethmoids in eight, and from the nasal cavity in another eight patients. Oncologic radicality of resection was verified by intraoperative frozen-section examination of biopsy specimens from the margins of the defect site.

Results

Radical resection was accomplished in 15 out of 16 operated patients. There were no major intra- or postoperative complications. Ten patients were postoperatively irradiated. Follow up of the treated patients ranged from 15 to 178 months (median 67 months). One patient with malignant melanoma died of generalized disease nine months after treatment, another with malignant melanoma recurred locally 30 months and again 49 months after first operation and is at the time of evaluation disease free and one died 21 months after operation without evidence of disease.

Conclusions

It seems that in selected cases, endoscopic surgery with curative intent for removal of malignant tumors of the nasal and paranasal cavities in the hands of highly experienced surgeon is justified.     

Optimization of treatment planning for radiation therapy

There are two problems to be solved to apply quantitative optimization for treatment planning of radiation therapy. Firstly, an objective function which estimates both biological effect of non-uniform dose distribution and dose response relationship has to be developed. Secondly, precise radiobiological and clinical data are required to derive and justify the objective function. Hence, it is important to decrease the errors in dose measurement and calculation and to clarify the factors in data analysis. In this article, the methods of optimization reported in the past were reviewed and some subjects for future studies were discussed.     

Conformal proton radiation therapy of the posterior fossa: a study comparing protons with three-dimensional planned photons in limiting dose to auditory structures

PURPOSE: Conventional radiation therapy for pediatric posterior fossa tumors can cause sequelae such as hearing loss and impairments in language and learning. Modern three-dimensional (3D) treatment techniques have improved dose conformity to the posterior fossa. This report compares the normal tissue dose-sparing capabilities of proton radiation therapy (PRT) with 3D conformal photon plans. METHODS AND MATERIALS: Nine children underwent previous PRT for primary CNS malignancies. Using original planning CT scans, the posterior fossa, inner and middle ear, and temporal lobes were delineated. Three-dimensional treatment plans were generated for protons and photons. Normal tissue exposures were calculated by averaging mean doses received and by analysis of dose-volume histogram. RESULTS: The 95% isodose encompassed the posterior fossa in all plans. Normal structures received markedly less radiation from PRT plans than from 3D photon plans. The cochlea received an average mean of 25 +/- 4% of the prescribed dose from PRT, and 75 +/- 6% from photons. Forty percent of temporal lobe volume was completely excluded using protons; with photons 90% of the temporal lobe received 31% of the dose. CONCLUSION: PRT resulted in increased dose sparing of normal structures analyzed. Posterior fossa conformity of 3D photons came at the expense of increasing amounts of normal tissue receiving low to moderate doses.     

The role of radiation therapy in inverted papilloma of the nasal cavity and paranasal sinuses

Between December 1969 and March 1985, seven patients with advanced biologically aggressive inverted or cylindrical cell papillomas were treated with irradiation at the University of Florida. Three patients were treated with radiation therapy alone, and four patients were irradiated either before (one patient) or after (three patients) resection. No recurrences were observed in six patients at 4.5, 7, 8, 8, 9, and 20 years following treatment (including two who died of intercurrent disease at 7 and 9 years after radiation therapy without evidence of recurrent tumor). One patient treated with irradiation alone for an advanced recurrent papilloma developed a local recurrence extending into the frontal lobe of the brain and died 17 months after radiation therapy. None of the patients experienced a significant complication of irradiation. Although surgery is generally the primary treatment modality for this disease, radiation therapy should be considered for patients with advanced, incompletely resected, or unresectable lesions.     

A quantitative study of MRI-based treatment planning for the percutaneous radiation therapy of brain tumors

This study examined to which extent treatment plans for brain tumors can be constructed with a commercial treatment planning system (TPS) based on MRI data only. CadPlan 6.4.7 was used as TPS. In particular, differences between MRT-based and conventional CT-based plans were examined systematically. The quantification of the retrospective evaluation was carried out by the point-wise dose difference and the gamma-distribution. In this study the gamma-distribution did not appear advantageous over the dose difference for the tolerance range (point-wise dose difference < 3%, distance criterion LLL 5 mm). The calculated dose distribution showed large differences (up to 103%) at the boundary of the treatment fields, in the regions of the head contour, and in areas with air inclusions and significant bone structures. The inner parts of the fields, and therefore the actual target volume, revealed only small deviations in the range of-2% in the homogeneous distribution.     

The influence of dose constraint point placement on optimized radiation therapy treatment planning

To efficiently use linear and quadratic programming for treatment planning optimization on a routine basis, automated methods are needed for placing dose constraint points. We have investigated, for linear programming optimization, the minimum number of constraint points needed to achieve an acceptable approximation to the desired (ideal) solution. Seven different constraint point placement algorithms were evaluated for a given objective function. One of these algorithms was chosen for routine clinical use at our institution. This algorithm places constraint points on the perimeter of the target volume and on the perimeter and in the interior of each normal structure. Additional points are placed on the perimeter of a constant thickness buffer region surrounding the target volume. Excellent optimization results are obtained with 40-70 constraint points per treatment planning slice.     

Alternative methods for intensity-modulated radiation therapy inverse planning and dose delivery

A large number of IMRT systems are currently being marketed. Many of these systems appear to be unique, and manufacturers often emphasize design differences as they argue the merits of their particular approach. This paper focuses on highlighting the underlying feature that is intrinsically part of all IMRT systems. On the other hand, major differences often appear at the implementation stage for dose delivery. Such variations are evident because each manufacturer has a unique approach to balancing the issues of treatment time, leakage radiation reaching the patient's total body, aperture approximation of the ideal intensity maps, increasing the angles of approach for the treatment fields, integration of on-line imaging, selection of treatment distance, availability of different photon energies, and overall system complexity (i.e., cost). How these different issues are handled in the process of system design affects the relative advantages and disadvantages that appear in the final product. This paper takes the approach of dividing the various IMRT methods into categories that are divided roughly along the lines of the technique used during dose delivery to approximate the intensity patterns. Other features of each system are included under these sub-sections.     

Computed tomography of malignant tumors of the nasal cavity and paranasal sinuses

Staging of malignant tumors of the nasal cavity and paranasal sinuses by computed tomography (CT) was studied in a total of 49 patients, 33 with squamous cell carcinoma and 16 with tumors of other histologic types. Involved sites by the tumor were studied, and clinical staging was made using CT findings alone according to AJC classification for maxillary sinus tumors. Surgical findings for comparison were available for most cases. Of 33 squamous cell carcinomas and of 16 tumors with other histologic types, the maxillary sinus was the site of origin in 29 and eight, respectively. Of these 37 maxillary sinus tumors, 11 were staged T3, 26, T4, and none was staged T1 or T2. None of these tumors were down staged, and one T3 was upstaged after surgical procedures, although all sinuses were not explored in some cases. Sinusitis due to obstruction was indistinguishable from the tumor without bone destruction. And the determination of the site of origin was difficult in some cases. Despite these, CT should be used for pretreatment evaluation of the tumors of these sites.     

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses—one esthesioneuroblas-toma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)—revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, I displayed a highly complex karyotype, including rearrangement of band 11 q 13, and I had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.     

Malignant salivary gland tumors of the paranasal sinuses and nasal cavity. The UCLA experience

Between 1962 and 1985, 35 patients with malignant salivary gland tumors of the paranasal sinuses and nasal cavity were treated with curative intent at UCLA. They were staged according to the American Joint Committee (TNM) classification for squamous cell carcinoma of the paranasal sinuses: 27 of 35 (77%) patients presented with T3-4 disease. Adenoid cystic carcinoma was the diagnosis in 24 (68%) patients, while adenocarcinoma accounted for half of the cases involving the ethmoid sinuses and nasal cavity. Eleven patients were treated with surgery alone, 13 with combined surgery and radiation, and 11 with radiation therapy alone. All patients were followed from 40 to 216 months. Analysis by treatment modality revealed a local control of 18% (2 of 11) in the surgery alone group, 62% (8 of 13) in the combined group, and 9% (1 of 11) in the radiation alone group. The group undergoing combined treatment achieved the highest local control rate despite having a higher proportion of patients with advanced stage and residual disease at the surgical margins. In patients with positive surgical margins, the tumor recurred locally in 4 of 6 (67%) unirradiated patients, compared with 3 of 10 (30%) of those undergoing postoperative irradiation. Patients with adenoid cystic carcinoma had poorer results, with only 25% remaining relapse-free, compared with 45% of patients with adenocarcinoma. The 5-, 10-, 15-, and 20-year actuarial survival for all cases was 73%, 60%, 32%, and 20%, respectively. We conclude that post-operative radiation improves the results of treatment in all patients with malignant salivary gland tumors in this location, compared with the results of surgery alone.     

CT scanning for radiation therapy treatment planning of hepatoma

One hundred forty-five patients with hepatoma had CT scanning for radiation therapy treatment planning. In order to demonstrate the anatomical distortions that occur with hepatoma and its effect on treatment planning, a control group of 50 colorectal cancer patients with normal livers was analyzed for comparison. The objectives of planning were to deliver as homogeneous a dose to the whole liver as possible and not to treat more than one of two functional kidneys or more than one-half of both functional kidneys. Conventional AP/PA portals were defined by physical examination, intravenous pyelogram, and bowel gas patterns at simulation and were found to be inadequate for the treatment of 76% of patients with hepatoma and 10% of patients with normal livers. Among the control group patients with no hepatoma, only 10% required oblique portals and 6% could not be treated because of left hydronephrosis or a solitary right kidney. Because the distortion of the liver in hepatoma in relationship to the kidneys required portal modification in 76% of hepatoma cases; 39% required oblique planning, 24% AP/PA, 20% PA and left lateral portals, and 17% required 4-field, 3-field or other plans in order to meet the treatment planning objectives. We concluded that all patients receiving radiation therapy to the liver for hepatoma require CT scanning for optimum radiation therapy treatment planning because of the hepatic distortion that occurs in hepatoma and the requirements of renal tolerance.     

Clinical evidence on PET-CT for radiation therapy planning in gastro-intestinal tumors

A large number of histological and anatomically distinct malignancies originate from the gastro-intestinal (GI) tract. Radiotherapy (RT) plays an increasing role in the multimodal treatment of most of these malignancies. The proximity of different organs at risk such as the kidneys, the spinal cord and the small bowel and the potential toxicity associated with combined treatment modalities make accurate target volume delineation imperative. The ability of positron emission tomography (PET) imaging to visualize a so-called ‘biological target volume’ (BTV) may be helpful in this respect. Currently the most widely used tracer for diagnosis, staging, restaging and response assessment is [¹⁸F]Fluoro-deoxyglucose (FDG). Promising preliminary results in esophageal, pancreatic and anorectal cancers and colorectal liver metastasis suggest that FDG-PET might provide us with additional information useful in target volume delineation. Poor image resolution and a low sensitivity for lymph node detection currently obstructs its widespread implementation. Moreover, validation in large prospective trials and the pathological validation of the correct tumor volume is still lacking. In hepatocellular carcinoma (HCC) and gastric adenocarcinoma there is currently little evidence for the use of FDG-PET in target delineation. However more extensive research is warranted before the true value of FDG-PET in these sites can be assessed. Also other tracers are constantly being developed and investigated. Up to now however none of these tracers has found its way into the daily practice of target volume delineation.     

Use of the functional imaging modalities in radiation therapy treatment planning in patients with glioblastoma

Glioblastoma multiforme still remains, at present, the most frequent and deadly primary malignant glioma in adult. Despite safer and larger neurosurgical resections, patients almost always relapse very close or inside the tumor bed. Since more than 20 years, radiation therapy (RT) continue delivering the same dose of 60 Gy in 6 weeks, more precisely guided with CT-scanner and magnetic resonance imaging (MRI) in the treatment position. If morbidity has decreased with "non whole-brain" volumes, RT is nearly always failing locally, as surgery. Until now, all the series evaluating escalating doses (up to 80-90 Gy) in limited volumes have failed. One can really question : is the good dose delivered in the adequate volume? Main goal of new imaging techniques is to better visualize microscopic extension of malignant glioma cells. As based on metabolic principles, areas of abnormalities visualized with functional imaging have a different meaning, often complementary from conventional data. The four evaluated techniques are : magnetic resonance spectroscoy (MRS), functional MRI (fMRI), 18FDG or methionine PET, IMT (123iodine-alpha-methyl-thyrosine) SPECT. Each technique has potential interests and limits, MRS and fMRI appearing the most promising : they have both acceptable spatial resolution and can be executed just after conventional MRI acquisition. Areas of functional abnormalities are only partially including areas of hyperintensity in T1, T2 weighted MRI. It is therefore highly possible that, using it complementary to conventional CT and MRI for RT treatment planning, they add some precious informations; consequently, the very limited efficacy/toxicity ratio could be increased. This hypothesis will only be confirmed by prospective studies registering in parallel both functional and morphological abnormalities, linking them with sites of local recurrence. Once "targeted" the real microscopically invaded areas, one can speculate on new escalating dose studies, delivering RT in "adequate" volumes, combining it with new "targeted" drugs, as already recently demonstrated in head and neck cancers.