Lung cancer management in limited resource settings: guidelines for appropriate good care.

Lung cancer is a major cause of cancer death worldwide and is becoming an increasing problem in developing countries. It is important that, in countries where health care resources are limited, these resources are used most effectively and cost-effectively. The authors, with the support of the International Atomic Energy Agency, drew on existing evidence-based clinical guidelines, published systematic reviews and meta-analyses, as well as recent research publications, to summarise the current evidence and to make broad recommendations on the non-surgical treatment of patients with lung cancer. Tables were constructed which summarise the different treatment options for specific groups of patients, the increase in resource use for and the likely additional clinical benefit from each option. These tables can be used to assess the cost-effectiveness and appropriateness of different interventions in a particular health care system and to develop local clinical guidelines.

The treatment of a large acoustic tumor with fractionated stereotactic radiotherapy.

The treatment of acoustic neuromas (AN) usually involves surgical excision or stereotactic radiosurgery. However, for large AN (mean diameter > 3 cm), stereotactic radiosurgery is rarely used, leaving patients with limited noninvasive treatment options. Recently, the use of fractionated stereotactic radiotherapy (FSRT) has been effective in treating small to medium-sized AN. We present a patient with a large AN treated with FSRT. The patient was a 43-year-old man presenting with imbalance, tinnitus, vertigo, and right-sided hearing decline associated with vomiting and hydrocephalus. Magnetic resonance (MR) imaging revealed a large, 3.8-cm, right cerebellopontine-angle tumor compressing the fourth ventricle. Following right frontal ventriculoperitoneal shunt placement, the patient underwent FSRT for treatment of the tumor. Using the Radionics X-Knife 4.0 3D treatment planning system, a total of 54 Gy was delivered in 1.8-Gy daily fractions with the prescription isodose line of 90%. Treatments were delivered using a dedicated Varian 6/100 linear accelerator, and head immobilization was achieved with the Gill-Thomas-Cosman relocatable stereotactic frame. The patient was subsequently evaluated with serial contrast-enhanced MR imaging. Following FSRT, local control (defined as the absence of tumor progression) was achieved, and treatment was well tolerated. There was no hearing-related, trigeminal, or facial-nerve morbidity following FSRT at 63-month follow-up. Treating a patient with a large AN with FSRT resulted in local tumor control, with no trigeminal nerve, facial nerve, or hearing-related morbidity. These results support FSRT as a potential noninvasive treatment modality for AN some would consider too large for single-fraction stereotactic radiosurgery (SRS).

Stereotactic radiosurgery versus fractionated stereotactic radiotherapy boost for patients with glioblastoma multiforme.

The aim of this study is to evaluate the efficacy of stereotactic radiotherapy boost (SRB) in patients with glioblastoma multiforme (GBM) by comparing two different regimens, single dose or fractionated treatment. Between December 1994 and January 2000, 24 patients with GBM were treated with SRB in conjunction with external beam radiotherapy (EBRT). Fourteen patients (58%) were treated with stereotactic radiosurgery (SRS) and 10 patients (42%) with fractionated stereotactic radiotherapy (FSRT). Median interval between EBRT and SRS or FSRT was 1.4 months (range -0.4-3.9 months). Actuarial survival rates of the entire 24 patients at one and two years following SRB were 63% and 34% respectively, with median survival time of 16 months. Variables predicting survival were age, extent of surgery, re-operation and the RTOG (Radiation Therapy Oncology Group) classes based on recursive partitioning analysis (RPA). In comparison to historical controls, improved survival benefit after SRB was observed. The median survival times for the RTOG classes 4, 5, and 6 were 28.3, 10.3, and 6.0 months following EBRT+SRB, respectively. Expected values for these classes after EBRT are 11.1, 8.9, and 4.6 months, respectively. This improvement in survival was seen predominantly for the RTOG class 4. There was no difference in survival between SRS and FSRT treated groups. Late complications developed in 4 patients in the SRS group and 1 patients in the FSRT group. Our retrospective data suggest that SRB in conjunction with EBRT may improve survival in patients with GBM with median survival time of 16 months, when compared to historical controls of the RTOG data following EBRT. The addition of SRB appeared to improve the median survival most demonstrably in RTOG RPA class 4 patients. SRS and FSRT are equally effective with similar median survival, but potentially less late complications associated with FSRT. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.

Linac-based stereotactic radiosurgery for treatment of trigeminal neuralgia.

Trigeminal neuralgia (TN) is a disabling pain condition that has classically been treated using either surgical or medical techniques. Several researchers have shown that stereotactically delivered radiation can be an effective tool in the amelioration of this condition. For these studies, the Gamma Knife was used to deliver the radiation treatment. The target location was designated as the proximal nerve at the root entry zone, and doses greater than 70 Gy to the maximum point in a single fraction were found to be effective in controlling pain in 80% of the patients treated. LINAC-based stereotactic radiosurgery has been notably absent from the treatment of TN, even though it has many similarities to Gamma Knife-based stereotactic radiosurgery. The aim of this paper is to describe our LINAC-based stereotactic technique for treatment of TN. We also compare treatment of TN using our technique to that using the Gamma Knife. We found that a LINAC-based treatment of TN can be accomplished with accuracy comparable to treatments delivered using the Gamma Knife. The dose distributions are essentially equivalent for the two treatment approaches. The LINAC-based system is easy to plan and offers the ability to reduce the involvement of sensitive structures from the treatment fields as well as the Gamma Knife system does. A disadvantage of the LINAC-based system is the time involved for treatment.

Radiation dose response for supratentorial low-grade glioma--institutional experience and literature review.

PURPOSE: To examine radiation dose response for low-grade glioma (LGG) based on our institutional experience and to review the literature on this topic. METHODS AND MATERIALS: Sixty-seven patients with supratentorial low-grade nonpilocytic astrocytomas (n=36) or oligodendrogliomas (n=31) were treated with postoperative radiation therapy (RT). Twenty-seven patients (group A) received 5520 cGy; 24 patients (group B) received 5940 cGy; and 16 patients (group C) received 6375 cGy. The corresponding median follow-up was 60, 35 and 91 months, respectively. RESULTS: The disease-specific survival (DSS) at 5 and 10 years were 90.2% and 56.2%, 67.6% and 47.3%, and 62.5% and 50% for groups A, B and C, respectively (P=0.40). Only a greater extent of surgical resection and absence of contrast enhancement predicted DSS on multivariate analyses. Patients receiving higher doses of RT had higher complication rates. CONCLUSION: Our data confirmed the lack of radiation dose response for supratentorial LGG as demonstrated in the previous randomized trials. The radiation dose should not exceed 5520 cGy because dose escalation did not result in an improvement of DSS and it also increased the complication rates. Future research should focus on the eradication of radioresistant clones either by the improvement of surgical resection or the use of cytotoxic agents that can target on the radioresistant tumor cells.

Changes in expression of transferrin, insulin-like growth factor 1, and interleukin 4 receptors after irradiation of cells of primary malignant brain tumor cell lines.

Various immunotoxins have been developed for the treatment of cancer. The toxin is internalized by target cells through cell-surface receptors, and it is essential for these receptors to be expressed for the immunotoxin to have specific anti-tumor activity. Radiation therapy is one of the main treatment modalities for primary malignant brain tumors. The purpose of this study was to determine whether radiation influences the expression of cell-surface receptors. Cells of one human medulloblastoma (Daoy) and two glioblastoma (U373-MG and T98-G) cell lines were tested by exposing the cells to a single dose of 5 Gy gamma rays. Expression of transferrin receptors, type-1 insulin-like growth factor receptors (IGF1R), and interleukin 4 receptors (IL4R) was measured by flow cytometry analysis on unirradiated cells and on cells 3 to 120 h after irradiation. In Daoy cells, the absolute expression index of transferrin receptors increased during the 24 h after irradiation with the greatest change of 26% above control at 9 h. The absolute expression index of IGF1R increased 26.5% above control at 12 h. The absolute expression index of IL4R decreased 9 h after irradiation. In U373-MG cells the absolute expression index of transferrin receptors increased during the 24 h after irradiation, and the greatest increase was 45% above control at 9 h. The absolute expression index of IGF1R increased during the 12 h after irradiation with a maximum increase of 33% above control at 6 h. The absolute expression index of IL4R decreased with time after irradiation. In T98-G cells, the absolute expression index of both transferrin receptors and IL4R decreased after irradiation. The results suggest that the expression of growth factor receptors on brain tumor cells may be influenced by radiation. The effect of ionizing radiation on receptor expression should be considered when administration of targeted toxin is combined with radiation. Similar studies with other growth factor receptors used in targeted toxin therapy are recommended.

Single dose versus fractionated stereotactic radiotherapy for meningiomas.

OBJECTIVE: To evaluate the safety and efficacy of stereotactic radiosurgery (SRS) compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas treated over a seven year period. METHODS AND MATERIALS: Of the 53 patients (15 male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18 patients with tumors adjacent to critical structures or with large tumors were treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy (500-4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63 months) respectively. RESULTS: The five-year tumor control probability (TC) for benign versus atypical meningiomas were 92.7% vs. 31% (P = .006). The three-year TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P = .62). For benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29 patients) vs. FSRT group (14 patients) respectively (P = .77). Two patients in the SRS group and one in the FSRT group developed late complications. CONCLUSION: Preliminary data suggest that SRS is a safe and effective treatment for patients with benign meningiomas. Fractionated stereotactic radiation therapy with conventional fractionation appeared to be an effective and safe treatment alternative for patients not appropriate for SRS. A longer follow-up is required to determine the long-term efficacy and the toxicity of these treatment modalities.