The Practice of Paediatric Radiation Oncology in Low- and Middle-income Countries: Outcomes of an International Atomic Energy Agency Study.

AIMS: Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' MATERIALS AND METHODS: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. RESULTS: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. CONCLUSIONS: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.

Anaplastic astroblastoma of childhood: aggressive behavior.

OBJECTIVE: Astroblastoma is an unusual brain tumor in childhood. Tumor usually arises from cerebral hemispheres. This large tumor is well-demarcated, lobulated, solid or cystic, and therefore, may resemble glioblastoma. Histopathologically, there are two types of astroblastoma: well-differentiated (low-grade) or anaplastic (high-grade). In low-grade astroblastoma, treatment of choice is complete excision. This type of tumor usually does not recur. However, anaplastic tumors can recur despite surgery, radiation, and chemotherapy and may be problematic for clinician. CASE REPORT: A 7-year-old female patient presented with an acute onset of vomiting and seizure. Magnetic resonance imaging study revealed a large mass in the left parieto-occipital region. She underwent total excision of the tumor. Histopathologically, the tumor was an anaplastic astroblastoma. Her adjuvant treatment was planned to consist of radiation therapy and cisplatin-based chemotherapy. However, the tumor recurred early in the course, and she died 18 months after diagnosis. CONCLUSION: High-grade astroblastomas behave like glioblastoma, as emphasized in this case report. Local control of this type of tumor seems difficult despite surgery, radiation therapy, and cisplatin-based chemotherapy.

Intraoperative extracorporeal irradiation and re-implantation of involved bone for the treatment of musculoskeletal tumors.

The purpose of this trial is to evaluate the results of musculoskeletal tumors which is treated with limb salvage surgery and extracorporeal radiotherapy. Patients were treated with en-bloc resection followed by 50 Gy single dose extracorporeal irradiation and re-implantation of involved bone segments. Nine of fifteen were female and 6 were male, median age was 19. Tumor originated from tibia in 7 patients, femur in 3, humerus in 3, calcaneus in 1 and scapula in 1. Preoperative chemotherapy was given to 12 patients, 3 of them had not been treated previously. Median follow-up time of the survivors was 22 months (range 2-47 months); local recurrence and lung metastases occurred in one patient (local recurrence was away from the re-implanted bone segment), and lung metastases were reported in another 3 patients. Wound healing problems occurred in 4 patients and delayed union in 2 patients. Amputation was performed in 2 patients due to uncontrolled infection, and infected bone was replaced by a fibula graft in another patient. Treatment was successful in 12 patients where functional results were good in 9, excellent in 2 and not evaluated in 1. Limb salvage using en-bloc resection followed by intraoperative extracorporeal irradiation and re-implantation of involved bone is a useful and cheap reconstruction method in appropriately selected patients.

Giant cell tumor of the bone with an asymptomatic huge solitary lung metastasis; case presentation and literature review.

A case concerning a man having giant cell tumor (GCT) of the leg and huge lung metastasis is presented. This case is discussed with a brief review of the relevant literature regarding detection and treatment of this care condition.

Second primary tumors in mycosis fungoides patients: experience at the Northern Israel Oncology Center (1979-2002).

PURPOSE: Mycosis fungoides (MF) patients enjoy longstanding remissions following total skin electron irradiation (TSEI) but run the risk of developing secondary malignancies. Our purpose was to report our experience with the phenomenon of secondary malignancies in MF patients. PATIENTS AND METHODS: From 1979 to 2002, 84 patients with biopsy-proven MF were referred to our department for TSEI, using the modified Christie Hospital translational technique until 1992 and the Stanford technique after 1992. Median total dose was 32 Gy (range 16-44) Christie; 30 Gy (range 15-36) Stanford. Underdosed areas were boosted with a median total dose of 10-20 Gy. RESULTS: During a median follow-up of 73 months (range 2-191) from the end of the TSEI, 12 (15%) patients developed 17 second primary tumors within the irradiated areas and 6 patients developed 7 second primary tumors, either simultaneously with the newly diagnosed MF or prior to introduction of radiation therapy. CONCLUSION: The long-term prognosis was related solely to the second primary. Due to excellent long-lasting response rates following TSEI coupled with long-term survival, and the prognosis mainly associated to the stage and histology of the second malignancy, physicians should be aware of the possibility of second primary tumors.

Neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin and followed by surgery in locally advanced non-small-cell lung cancer.

Thirty-seven patients were enrolled in a phase II study to evaluate the efficacy and toxicity of neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin in locoregionally advanced non-small-cell lung cancer (NSCLC). The study was also designed to evaluate the operability following concurrent chemoirradiation. The following response rates to chemoirradiation were obtained: complete response (CR) 5 of 37 (13.5%), partial response 14 of 37 (38%), stable disease 12 of 37 (32.5%) and PD 6 of 37 (16%). Twenty patients underwent surgery, and in 19 patients the tumor was totally resected. There was pathologic CR in 4 patients. Moderate/severe esophagitis developed in 16 patients (43%); hematologic toxicity was mild. There was one case of postoperative mortality. Nine patients are alive without evidence of disease at 5+ to 39+ months. Median survival is 22 months. It is concluded that neoadjuvant radiotherapy concurrent with weekly paclitaxel/carboplatin is effective and well tolerated in patients and feasible for patients with locally advanced NSCLC, allowing complete tumor resection in 56% of the cases.

High-dose epirubicin and cisplatin in locally advanced undifferentiated nasopharyngeal carcinoma.

AIM: Undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive tumour; a randomized study evaluating neoadjuvant chemotherapy with bleomycin/epidoxorubicin/cisplatin (BEC) in addition to conventional radiotherapy has resulted in a better disease-free survival in the chemotherapy arm. The bleomycin infusion in the BEC regimen has necessitated hospitalization for the infusion, and resulted in serious pulmonary toxicity. This study has aimed to omit the bleomycin, and test the efficacy and toxicity of cisplatin (C) and a higher dose of epidoxorubicin (EPI) in patients with locally advanced UNPC. METHODS: Seventy-one patients with locally advanced UNPC were treated with three cycles of C 100 mg/m2 day 1, and EPI 100 mg/m2 day 1 every 3 weeks followed by conventional radiotherapy of 70 Gy. RESULTS: Neoadjuvant chemotherapy was well tolerated. There was only 1-week delay in 14.3% of the patients and no dose modification. Grade III-IV neutropenia occurred in 18.9% of the cycles: none of the patients developed neutropenic fever. No patient progressed during chemotherapy, the complete response rate was 26.8% (95% CI = 16.9-38.6) and the partial response rate was 59.1% (95% CI = 46.8-70.7) for an objective response rate of 85.9% (95% CI = 75.6-93.0) at the end of the three cycles of chemotherapy. After the completion of radiotherapy, the complete response rate increased to 81.7% (95% CI = 70.7-89.9) and the objective response increased to 91.5% (95% CI = 82.5-96.8). The median disease-free interval and the median survival have not been reached. The 5-year disease-free and overall survival rates are 53.0% (95% CI = 43.7-62.0) and 57.2% (95% CI = 48.3-65.2), respectively. CONCLUSION: Neoadjuvant C and EPI, easily administered in the outpatient setting, is an effective and well-tolerated regimen in the treatment of locally advanced UNPC.

Total skin electron irradiation in mycosis fungoides: comparison between a modified Christie Hospital translational technique and the Stanford technique.

Seventy-one patients with mycosis fungoides (MF) were treated by Total skin electron irradiation (TSEI) using either a modified Christie Hospital translational technique (44 pts) or a six dual-field Stanford technique (27 pts). There was no statistical difference in response rate, disease-free survival and overall survival between the two irradiation techniques. However, the Stanford technique was significantly less toxic than the modified Christie Hospital technique.

Primary osteosarcoma of the sphenoid bone with multiple recurrences: a case report and review of the literature.

In this paper a patient with primary osteosarcoma of the sphenoid bone, which recurred twice following surgery and was managed with re-excision, irradiation and chemotherapy is presented due to its extremely rare presentation and atypical course. The relevant literature is also reviewed.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION: A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS: Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS: Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS: It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.

Late radiation effects to the rectum and bladder in gynecologic cancer patients: the comparison of LENT/SOMA and RTOG/EORTC late-effects scoring systems.

PURPOSE: To test the correlation of LENT/SOMA and RTOG/EORTC late-effect scales for rectum and bladder, 116 cases with gynecologic malignancies that were treated with radiotherapy were assessed with both scales. METHODS AND MATERIALS: All cases had been treated at least 6 months before the date of assessment with external beam radiotherapy (50--54 Gy to midline) and 1--2 fractions of HDR brachytherapy (2 x 8.5 Gy to point-A for 32 inoperable cases; 1 x 9.25 Gy to 5--9 mm from the ovoid surface for 84 postoperative cases). The patients were questioned with both scales, and the correlation between the two scales was analyzed by Spearman's rho (rank correlation) test. RESULTS: There were 64 cases with uterine cervix carcinoma and 52 cases with endometrium carcinoma, The overall (external + brachy) doses to ICRU points were 57.8 +/- 3.8 Gy for rectum and 59.3 +/- 4.9 Gy for bladder. The statistical analysis of LENT/SOMA and RTOG/EORTC scales revealed a very good correlation for rectum (r = 0.81; p < 0.01) and a good correlation for bladder (r = 0.72; p < 0.01). CONCLUSION: The LENT/SOMA system is a further step on the reporting of late radiation effects. Some modifications will improve its precision, and multicentric randomized studies are needed to test its validity.

Postoperative radiotherapy in endometrial carcinoma: analysis of prognostic factors in 440 cases.

PURPOSE: The aim of this study was to determine the prognostic factors influencing overall, disease-free and local recurrence-free survival in patients treated postoperatively with adjuvant radiotherapy for endometrial carcinoma. METHODS: The records of 440 patients with endometrial carcinoma treated by postoperative radiotherapy between January 1985 and June 1997 were reviewed retrospectively. All patients received postoperative external radiotherapy with 1.8-2.0 Gy daily fractions up to 36-68 Gy (median 54 Gy). Intracavitary brachytherapy was applied to 61.8% of the cases. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. RESULTS: Median age of the patients was 57 (range: 35-83). Histologically 80.2% were adenocarcinoma, 5.7% adenosquamous carcinoma, 5.2% clear-cell carcinoma and 4.3% serous papillary carcinoma. The distribution by stages were: 62.2% Stage I, 20.0% Stage II, 14.9% Stage III, 2.8% Stage IV. Median follow-up time was 53 months (7-173 months). Total failure rate was 15.2% with 2.7% of patients having only local failure, 2.0% local and distant failure and 10.5% distant failure only. Five-year overall, disease-free and local recurrence-free survival rates were 81.6%, 80.7% and 94.6%, respectively. According to univariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0067), histologic grade (p=0.0015), stage (p<0.0001), myometrial invasion (p<0.0001), peritoneal cytology (p=0.0013) and cervical involvement (p=0.0106) while the prognostic factors affecting local recurrence-free survival were stage (p=0.0277), myometrial invasion (p=0.0054), peritoneal cytology (p=0.0427). According to multivariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0194), myometrial invasion (p=0.0021), and histologic grade (p=0.0303) while the only prognostic factor influencing local recurrence-free survival was myometrial invasion (p=0.0241). CONCLUSION: Radiotherapy is a highly effective adjuvant treatment providing an excellent locoregional control rate and it should be continued for patients with unfavorable prognostic factors.

Effect of geometrical optimization on the treatment volumes and the dose homogeneity of biplane interstitial brachytherapy implants.

BACKGROUND AND PURPOSE: The isodose distributions of HDR stepping source brachytherapy implants can be modified by changing dwell times and this procedure is called optimization. The purpose of this study is to evaluate the effect of geometrical optimization on the brachytherapy volumes and the dose homogeneity inside the implant and to compare them with non-optimized counterparts. MATERIAL AND METHODS: A set of biplane breast implants consisting of 84 different configurations have been digitized by the planning computer and volumetric analysis was performed for both non-optimized and geometrically optimized implants. Treated length (TL), treated volume (V100), irradiated volume (V50), overdose volume (V200) and quality index (QI) have been calculated for every non-optimized implant and compared to its corresponding geometrically optimized implant having a similar configuration and covering the same target length. RESULTS: The mean TL was 74.48% of the active length (AL) for non-optimized implants and was 91.87% for optimized implants (P < 0.001). The mean QI was 1.83 for non-optimized implants and 2.17 for optimized implants (P < 0.001). The mean V50/V100 value was 2.71 for non-optimized implants and 2.65 for optimized implants (P < 0.001) and the mean V200/V100 value was 0.09 for non-optimized implants and 0.10 for optimized implants (P < 0.001). CONCLUSIONS: By performing geometrical optimization it is possible to implant shorter needles for a given tumour to adequately cover the target volume with the reference isodose and thus surgical damage is reduced. The amount of healthy tissues outside the target receiving considerable radiation is significantly reduced due to the decrease in irradiated volume. Dose homogeneity inside the implant is significantly improved. Although there is a slight increase of overdose volume inside the implant, this increase is considered to be negligible in clinical applications.

The value and limitations of 201Tl scintigraphy in the evaluation of lung lesions and post-therapy follow-up of primary lung carcinoma.

In this study 201Tl planar scintigraphy and single photon emission computed tomography (SPECT) were performed in 92 patients with solitary lung lesions in order to distinguish malignant versus benign and metastatic masses and to evaluate the radiotherapy response of 15 primary lung carcinomas. Semiquantitative and quantitative analyses were carried out and the results were compared with histopathological diagnosis. The overall sensitivity, specificity and accuracy of semiquantitative analysis were 56, 71 and 58%, and quantitative evaluations were 88.8, 100 and 92%, respectively. Retention indexes (RI) derived from the early and delayed images were 2.9 +/- 1.3 for primary lung carcinomas, -2.78 +/- 0.9 for benign conditions and -2.3 +/- 1.5 for metastatic pulmonary lesions. 201Tl scintigraphy seems to be a sensitive modality for differentiating malignancies from benign conditions since the difference between those two pathologies is significant. However, this procedure has a limited value in distinguishing metastatic pulmonary lesions from benign pathologies, and in tissue characterization of primary lung carcinomas. On the other hand, a good correlation was observed between 201Tl lung scintigraphy and clinical diagnostic examination during postradiotherapy follow-up of inoperable pulmonary neoplasia.