Radiation therapy outcome

Harrison LB, Chadha M, HiU RJ, Hu K, Shasha D (2002) Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist 7 492 508... 

Cancer treatments have exploded technologically in the last couple of decades. The fields of radiation therapy, surgery, and pharmaceuticals have had numerous developments, so patients are receiving not only less toxic treatments but also treatments that have improved outcomes over those of 15 years ago. Supportive-care therapies have improved, so patients may be at... 

Androgen ablation with a luteinizing hormone-releasing hormone (LHRH) agonist plus an antiandrogen should be used prior to radiation therapy for patients with locally advanced prostate cancer to improve outcomes over radiation therapy alone. 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

Curran WJ Jr, Scott CB, Horton J, et al. Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF) A report of 3 Radiation Therapy Oncology Group trials. JNeurooncol 1992 12 219-227. 

The median follow-up was 23 mo for the 1073 evaluable patients. Patients that received hyperfractionated or accelerated radiation therapy with boost had increased locoregional control (p = 0.045 and p = 0.05, respectively) and a trend toward improved disease-free survival (DFS) (p = 0.067 and p = 0.054, respectively) in comparison to conventional radiation therapy. However, there was no improvement in overall survival(s). Patients given accelerated split-course fractionation had similar outcomes to those who had received conventional radiotherapy. Hyperfractionated radiation therapy is the method of choice for combined chemoradiotherapy in current investigative approaches for head and neck cancer. 

Langer C, Scott C, Byhardt R, et al. Effect of advanced age on outcome in Radiation Therapy Oncology Group studies of locally advanced NSCLC. Lung Cancer 2000 29(Suppl 1)104 A-340. 

Unfortunately, none of the seven randomized trials that have compared radiation therapy alone vs neoadjuvant cisplatin-containing chemotherapy plus radiation therapy demonstrated an improvement in overall or disease-free survival with combined-modality therapy (Table 2). Two studies actually demonstrated poorer survival with neoadjuvant chemotherapy. Souhami et al. (15) reported a significantly poorer survival rate with neoadjuvant chemotherapy in a small trial of patients with stage IIIB disease. This outcome was partly due to increased toxicity and poor compliance in patients who received chemotherapy. Another trial of neoadjuvant epirubicin and cisplatin was closed early when interim analysis revealed a significantly higher recurrence rate in the chemotherapy arm (16). These trials fail to provide any evidence that sequential cisplatin-containing chemotherapy and radiation therapy are of benefit. Possible explanations for the disappointing results include the effects of chemotoxicity, altered compliance, and possible accelerated repopulation of resistant clones after neoadjuvant chemotherapy. 

The literature strongly suggests that concurrent chemoradiation is superior to neoadjuvant chemotherapy followed by radiation therapy. However, the effect of continuing chemotherapy after radiation is complete is uncertain. Two of the positive trials (the SWOG postoperative trial [19] and a study of concurrent epirubicin [28J) involved additional cycles of chemotherapy after concurrent chemoradiation was completed. In their report, Peters et al. (19) suggested that postradiation chemotherapy contributed importantly to their patients good outcomes because those who completed the full course of treatment appeared to have a better outcome than those who received only the concur-... 

Mehta, M.P. et al. (2003) Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases, J. Clin. Oncol. 21, 2529-2536. 

CondadoJA, Waksman R, Gurdiel O, etal. Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans. Circulation 1997 96 727-732. 

Waksman R, Cheneau E, Ajani AE, et al. Intracoronary radiation therapy improves the clinical and angiographic outcomes of diffuse in-stent restenotic lesions results of the Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST) Studies. Circulation 2003 107 1744. 

About 14000 patients with the disease ankylosing spondylitis received X-ray therapy between 1935 and 1954 in Great Britain and Northern Ireland. In irradiating the spine, doses of 300-700 rad were received by tissues in the thoracic region. The major radiation-related outcome has been an excess of leukemia due to irradiation of bone marrow progenitor cells within the ribs and vertebrae and, recently, an indication of excess solid tumors in the lungs,... 

The randomized controlled trial (RCT) is the de facto standard for studies of the health effects of medical interventions. In these studies, patients are randomized to receive either a therapy to be tested or an alternative (either a placebo or a conventional treatment), and an outcome is measured. RCTs have been used to evaluate therapeutic interventions, including drugs, radiation therapy, and surgical interventions, among others. The measured outcomes vary from hard evidence, such as mortality and morbidity, to softer evidence, such as patient-reported satisfaction and surrogate end points typified by markers of disease activity... 

Mitomycin is an alkylating antibiotic that produces pulmonary fibrosis at a frequency of 3% to 12%. The mechanism is unknown, but oxygen and radiation therapy appear to enhance the development of toxicity. The clinical presentation and symptoms are the same as for bleomycin. The mortality rate is about 50%. Early withdrawal of the drug and administration of corticosteroids appear to improve the outcome significantly. 

Regine WF, Scott C, Murray K, et al Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs accelerated-hyperfractioned radiotherapy an analysis from Radiation Therapy Oncology Group Study 91-04. Int J Radiat Oncol Biol Phys 51 711-717, 2001... 

Figure 18.9 Apoptosis resistance is a hallmark of cancer. Multiple genetic lesions results In an Increased apoptotic threshold that accompanies the cancerous phenotype. The relative resistance of cells to apoptosis Is Indicated by the thickness of the arrow and the key genes involved In setting the apoptotic threshold are shown. The function of these genes can be affected by either genetic mutations (such as loss of heterozygosity, LOH) or direct inhibition of their function by cellular Inhibitors (such as Bcl-2, lAP, or heath shock (HSP) proteins). The ultimate outcome is the inability of cancer cells to undergo apoptosis despite exposure to potent cell death triggers (such as In case of therapeutic inten/ention with chemo- or radiation therapy).

I. Gage, A. Recht, R. Gelman, A.J. Nixon, B. Silver, B.A. Bomstein, J.R. Harris (1995). Long-term outcome following breast-conserving surgery and radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 33(2), 245-251. 

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