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.

Need for radiotherapy in low and middle income countries ­ the silent crisis continues.

About 57% of the total number of cancer cases occur in low and middle income countries. Radiotherapy is one of the main components of cancer treatment and requires substantial initial investment in infrastructure and training. Many departments continue to have basic facilities and to use simple techniques, while modern technologies have only been installed in big cities in upper-middle income countries. More than 50% of cancer patients requiring radiotherapy in low and middle income countries lack access to treatment. The situation is dramatic in low income countries, where the proportion is higher than 90%. The overall number of additional teletherapy units needed corresponds to about twice the installed capacity in Europe. The figures for different income level groups clearly show the correlation between gross national income per capita and the availability of services. The range of radiotherapy needs currently covered varies from 0% and 3-4% in low income countries in Latin America and Africa up to 59-79% in upper-middle income countries in Europe and Central Asia. The number of additional radiation oncologists, medical physicist, dosimetrists and radiation therapists (RTTs) required to operate additional radiotherapy departments needed is 43 200 professionals. Training and education programmes are not available in every developing country and in many cases the only option is sending trainees abroad, which is not a cost-effective solution. The implementation of adequate local training should be the following step after establishing the first radiotherapy facility in any country. Joint efforts should be made to establish at least one radiotherapy facility in countries where they do not exist, in order to create radiotherapy communities that could be the base for future expansion.

Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Chronic total occlusion due to diffuse in-stent restenosis: is brachytherapy the solution?

Percutaneous coronary intervention of chronic total occlusions (CTO) is associated with a significantly higher incidence of reocclusion and restenosis compared with non-total occlusions. Randomized and observational trials have demonstrated the effectiveness of intracoronary brachytherapy (ICBT) for the prevention of recurrent in-stent restenosis. However, limited data are available on the effectiveness of ICBT in patients with totally occluded in-stent restenosis. The authors assessed the long-term outcome of patients treated with intracoronary gamma radiation for totally occluded in-stent restenotic lesions. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 100 patients (103 vessels) with diffuse in-stent restenosis. At baseline, CTO of the target vessel at the site of the stent was present in 15 vessels (14.5%). Follow-up data were collected during follow-up visits and from telephone interviews. Repeat coronary angiography was performed in symptomatic patients with clinical restenosis. Clinical and angiographic characteristics were similar between the two groups, although there was a trend towards more unstable angina at the index procedure in CTO patients (66.7% versus 41.4%; p = 0.12) compared with patients without non-total occlusions. A higher percentage of patients (53.3%) with CTO required longer radiation sources (14 seeds, covering a length of 55 mm), compared with 23.9% of patients with non-total occlusion (p = 0.04). With a mean follow-up period of 47.5 +/- 24.0 months, major adverse cardiac events (MACE) were observed in 10 of 15 patients (66.7%) with CTO compared with 25 out of 88 patients (28.4%) without CTO (p = 0.009). According to multivariate analysis, total occlusion of the target vessel at baseline was the single independent predictor of MACE at one-year follow-up (relative risk 16.2, 95% confidence interval 4.2-62.9; p < 0.0001). This study shows that the use of gamma radiation for the prevention of recurrence of in-stent restenosis in patients with CTO does not seem to be as effective as in patients with non-total occlusions. Furthermore, CTO was an independent predictor of worse outcome at long-term follow-up in this study.

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.

Implementing a tantalum wire mesh to increase the skin dose in low-energy electron irradiation of the chest wall.

Radiation treatment of the post-mastectomy chest wall is performed in our institution by straight-on electron irradiation. The chest-wall thickness is measured and the beam energy is chosen so that the chest wall is treated to therapeutic doses, while sparing the underlying lung tissue. The most commonly chosen energies are 6 and 9 MeV. The skin dose should be 90% of the dose prescribed to the chest wall, which is higher than can be achieved with 6- and 9-MeV beams because of the low surface dose. The addition of a bolus slab during part of the treatment can correct for this; however, the added depth means that a higher energy has to be chosen, which will increase the lung dose (the higher the electron energy, the slower the falloff of the electron depth-dose curve). A mesh of a high-Z material above the skin gives rise to obliquely scattered and low-energy electrons that effectively spoil the buildup zone. Dosimetric measurements of a Tantalum (Ta) mesh were performed using a dose scanner in a water tank and a film inserted in a humanoid phantom during a simulated treatment. Measurements were also done for the clinically relevant cases of oblique beam incidence and with the mesh placed 1 cm above the surface. The measurements demonstrate the spoiling of the buildup zone, while having only a moderate influence on the dose distribution beyond the dose maximum. The mesh also changes the absolute dose. In a fractionated regime, the first part of the treatment would be without the mesh, adding it only during the latter fractions. The total dose distribution gives 90% to the skin, while leaving the depth-dose characteristics beyond the dose maximum virtually unchanged.

High-dose-rate endobronchial brachytherapy in endobronchial metastatic malignant chondroid syringoma.

A 65-year-old man with malignant chondroid syringoma (MCS) was found to have pulmonary metastases in the form of multiple pulmonary nodules 4 years after wide excision and adjuvant radiotherapy of a primary abdominal wall tumor. Atelectasis of the lingula due to obstructive endobronchial metastasis, resistant to combination chemotherapy, led us to perform high-dose rate (HDR) endobronchial brachytherapy for the first time in this rare tumor with a favorable response. This case emphasizes the role of HDR brachytherapy as a palliative procedure in endobronchial tumors not responding to other treatment modalities, even those considered to be radioresistant.

Epstein-Barr virus and cancers of the head and neck.

Denis Burkitt pioneered the association of viruses and cancer in humans with his observations of lymphomatous tumors in children in equatorial Africa. The Epstein-Barr virus (EBV), a human B lymphotrophic herpes virus, is strongly associated with undifferentiated carcinoma of the nasopharynx and African-type Burkitt's lymphoma. More recently, an association of this virus with other epithelial neoplasms, lymphomas, and immunodeficiency-related malignant and nonmalignant conditions has been reported. Since many of these tumors are rare, much of the information is based on sporadic reports and relatively small series of patients. The purpose of this report is to review the literature and examine the growing association of EBV with various head and neck malignancies.

Telephone triage. A common sense approach.

Can you accurately assess a patient's condition over the telephone? Can you determine which patients should be seen in the ED or the office, and which patients can follow your advice for home treatment? Telephone triage can save time and money--if it's done effectively.

[Preservation of the larynx in advanced cancer--experiences at the Oncology Department, Rambam Medical Center, Haifa].

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m2) and 5-fluorouracil (1000 mg/m2/day) as a continuous infusion on days 1-5, followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons. 19 of the 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response, and in 5 tumor recurrence. Mean survival was 39 months (range 11-46 months); at last follow-up, 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 had died due to disease progression and due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

Low dose-rate interstitial brachytherapy in soft tissue sarcomas.

Purpose. To assess the effectiveness of Ir-192 interstitial brachytherapy as an adjunct to wide local excision as a functionsaving strategy for soft tissue sarcomas.Subjects and methods. From September 1993 to April 1998, 20 consecutive patients diagnosed with soft tissue sarcomas were treated with a combination of wide local excision and interstitial brachytherapy. In 16 patients brachytherapy was done as an intraoperative procedure, while in four, the implant was performed post-operatively under local anesthesia. Eleven of the 20 patients also received external beam radiotherapy following the implant.Results. After a mean follow-up of 27 months (4-54) the local control rate for all 20 patients was 85% (17/20). In the 16 patients who had an intra-operative implant, local control was 94% (15/16). In the four patients who underwent a post-operative implant, local control was 50% (2/4). Actuarial 5-year survival was 90%. There were three cases (15%) of severe local complications.Conclusions. Wide local excision followed by low dose rate intersitital brachytherapy have yielded a 85% local control rate in 20 patients with soft tissue sarcomas. Local control rates were higher when the implants were done as an intra-operative procedure than as a post-operative one.

Total skin electron irradiation in mycosis fungoides dose and fractionation considerations.

This study was undertaken to analyze the influence of total skin dose and dose-fractionation schedules on the response rate, survival and skin toxicity of patients with mycosis fungoides [MF] treated with total skin electron irradiation [TSEI]. From 1979 to 1992, 40 patients with MF were treated with TSEI using a modified Christie Hospital technique. Mean follow-up time was 48 months [median 20 months]. 37/40 patients completed TSEI; three died due to non-treatment-related conditions during therapy. 34/37 [92%] treated patients achieved complete remission [CR] and 16/40 [40%] are alive with no evidence of disease. Over the years, changes in dose-fractionation schedules were made and correlated with the pattern of CR and skin toxicity. The 5-year actuarial survival [Stanford staging] was 84% in Stages IA-IB [all Stage IA patients are alive] and 59% in Stage II. The probability of survival of Stage III-IV patients was 30% at 30 months. Late skin toxicity was mild to moderate in 60% and severe in 25% of patients. A reduction of the total dose and dose-per-fraction resulted in an acceptable CR rate and a significantly lower toxicity. TSEI is effective in early stage MF. Skin control and late skin toxicity seem to be dose-fractionation-schedule related. For the early stages, the optimal treatment schedule seems to be 24-30 Gy to the whole skin surface in 2.4-3.0 Gy fractions, given twice weekly over a period of four to six weeks. Total doses of 24-30 Gy at 2.4-3.0 Gy per fraction yielded comparable skin control rates with lower skin toxicity.

A simple oral cone attachment for the Varian linear accelerator.

Lesions in the oral cavity are often treated with two opposed lateral fields. These include a significant amount of normal healthy tissue whose radiation tolerance is dose-limiting. The tumor dose can be boosted to tumorcidal levels by brachytherapy or by small electron fields directed straight on the lesion. We have developed a simple attachment to the standard electron applicator of the Varian Clinac 1800 that allows irradiation of small electron fields through acrylic tubes-the oral cones. These tubes have been evaluated in terms of depth dose and field profiles for 6, 9, 12, 16, and 20 MeV electrons using film for relative dosimetry. At these small field sizes there are significant changes in output factors, in the depth dose as well as in the effective size of the field, and a thorough dosimetric evaluation is imperative prior to treatment. The attachment can be manufactured locally at low cost. For reasons of patient safety the assembly is collapsible. In clinical practice the cone is directed directly on the tumor. For deep-seated lesions we use a penlight and a mirror for positioning.

Intensive chemotherapy using cisplatin and fluorouracil followed by radiotherapy in advanced head and neck cancer.

This protocol was designed to achieve an improvement in the overall and disease-free survival in locally advanced, previously untreated carcinoma of the head and neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and one of unknown origin were treated with intensive chemotherapy followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of two cycles of cisplatin 100 mg/m2 over 60 min on day 1, plus 5FU 1000 mg/m2 continuous infusion over 24 h on days 2-5, with a 10-day interval between the two cycles, followed by definitive radiotherapy after 10 days. The overall response rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51% partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With a median follow-up period of 48 months, the 5-year actuarial survival and disease-free survival rates were 67% and 45%, respectively. No difference was found in the survival probability of pts with carcinoma of the nasopharynx, larynx or other primary sites. The survival of pts with a performance status (PS) < or = 1 was better than pts with PS > 1, 72% versus 51% (not significant). The survival probability of complete responders to chemotherapy was superior than the survival of non-complete responders to chemotherapy, 100% versus 54% [P = 0.001]. The main toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen demonstrated a high CR rate and survival probability in pts with locally advanced and mostly inoperable head and neck cancer.

Children's understanding of the meaning and functions of verbal irony.

We investigated children's understanding of irony and sensitivity to irony's meanness and humor. In Study 1, 89 participants (5-6-year-olds, 8-9-year-olds, adults) heard ironic and literal criticisms, and literal compliments. Comprehension of irony emerged between 5 and 6 years of age. Ratings of humor increased with age; ratings of meanness did not (showing that all ages perceived irony as more muted than literal criticism). In Study 2, results from 135 participants (6-7-year-olds, 8-9-year-olds, and adults) replicated these findings and revealed the role of form and intonation. Thus, comprehension of irony emerges between 5 and 6 years of age, and sensitivity to the muting function develops prior to sensitivity to the humor function.

Reduction of the rectal dose in gynecological brachytherapy: modification to the Fletcher-Suit applicator.

The dose to the anterior rectal wall is a known limiting factor for the delivery of radical doses of radiation to the uterine cervix with brachytherapy. We developed a modification to the Fletcher-Suit afterloading applicator, consisting of two small inflatable balloons attached to the posterior end of each colpostat. The balloons are connected to catheters that emerge from the vagina attached to the colpostat's handles. The balloons were affixed to the colpostats with a plastic adaptor and are inserted empty. After an anterior radiograph is taken, the balloons are filled with radiological contrast material and a lateral orthogonal film is made. This lateral film taken with the balloons filled with contrast typically shows a significant posterior displacement of the anterior rectal wall away from the vaginal sources. The International Commission on Radiation Units (ICRU) rectal point is then determined 5 mm beyond the posterior boundary of the opacified balloons. We have performed 90 applications using this device, including brachytherapy applications for cervical cancer, as well as vaginal applications for endometrial carcinoma following TAH-BSO. On average, the ICRU rectal point was displaced 14 mm away from the colpostats, thus reducing the dose rate by 60% and resulting in an average dose sparing of about 1000 cGy to the anterior rectal wall.

Choosing the best protective gloves.

Gloves should provide two-way protection from the transmission of microorganisms between worker and patient. Until recently, glove manufacturers paid little attention to barrier properties. Because the operating room is a high-risk area, surgical nurses must be especially careful about gloving practices.