External beam radiation

Local therapy of early-stage breast cancer consists of modified radical mastectomy or lumpectomy plus external-beam radiation therapy. The surgical approach to the ipsilateral axilla may consist of a full level I/II axillary lymph node dissection or a lymph node mapping procedure with sentinel lymph node biopsy. 

In most instances, external-beam radiation therapy used in conjunction with breast-conserving procedures involves 4 to 6 weeks of radiation therapy directed to the breast tissue to eradicate residual disease. Complications associated with radiation therapy to the breast are minor and include reddening and erythema of the breast tissue and subsequent shrinkage of total breast mass beyond that predicted on the basis of breast tissue removal. Some clinical situations also require postmastectomy radiation therapy as well (see section on locally advanced breast cancer). 

Radiation therapy The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monodonal antibody, that circulates throughout the body. Also called radiotherapy, [nih]... 

Langer CJ, Paulus R, Ruffer J, Movsas B, Murray K, Rhodes H, Curran WJ. Pro Am Soc Clin Oncol. Phase IIRTOG Trial of Weekly Paclitaxel (TAX) and Conventional External Beam Radiation Therapy for Supratentorial Glioblastoma Mutiforme (abstract 534) 1999. 18. 

S af ar AM, Altamiro PS, Recht A, et al. Phase I trial of gemcitabine, cisplatin and external beam radiation therapy for pancreatic cancer. Proc Am Soc Clin Oncol 1999 18 227a. 

Langer CJ, Ruffer J, Rhodes H, et al. Phase II Radiation Therapy Oncology Group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2001 51 113-119. 

Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207) final report. Cancer 2000 88(5) 988-995. 

Androgen deprivation therapy (ADT) is being used increasingly as neo-adjuvant and adjuvant therapy. Neo-adjuvant ADT for 4-6 months before external beam radiation can enhance survival and reduce the prostate volume to be irradiated. Similar benefits have not been seen prior to radical prostatectomy. The benefits of neo-adjuvant therapy are most evident for high risk localized prostate cancer. Adjuvant ADT for up to 2 years following external beam radiation increases disease-free survival and overall survival for locally advanced (T3) tumors. 

Particles emitted from radioactive isotopes are generally too low in energy to provide the penetration required for conventional treatments of tumors with external radiation beams. Most external beam radiation therapies are performed with high-energy x-rays or electrons produced with compact linear accelerators with accelerating potentials between about 4 and 20 MeV. One notable exception is certain devices designed for stereotactical radiosurgery or radiation therapy of superficial tumors that use cobalt-60 y-rays. The... 

Gastrointestinal effects are common when flutamide is used to treat advanced cases of prostate cancer. At doses of 250 mg every 8 hours or 500 mg/day, 23 of 106 men had gastrointestinal problems, irrespective of the dosage regimen (45). There was no difference in the incidence of these effects in the 56 men who had previously received external beam radiation and 50 others who had undergone radical prostatectomy. This suggests that the gastrointestinal adverse effects of flutamide are not due to a local toxic effect. 

The first clinical human trials using magnetic hyperthermia were reported by Liibbe, et al. [70, 129, 137, 190] who used 100-nm starch-coated iron-oxide particles bound with epirubicin for treatment of advanced solid cancers. Jordan recently reported positive results from ongoing trials of advanced cancer patients who received magnetic nanoparticle hyperthermia in conjunction with conformal external beam radiation therapy [191]. The therapy was well tolerated by the patients and significant increases in the length and quality of life were observed. 

International Agency for Research on Cancer has determined that radioactive strontium is a human carcinogen. Sr has been explored as an anticancer treatment, for example, for prostate cancer, and has been used as palliative treatment for patients with bone pain from osseous metastases. Excellent clinical responses for bone pain treatment have been observed (acceptable hematologic toxicity and clinical results rival those of external beam radiation therapy). 

Akakura A, Isaka S, Akimoto S, et al. Long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer Radical prostatectomy versus external beam radiation with a common endocrine therapy in both modalities. Urology 1999 54 313-318. 

External beam radiation used as sole therapy or in combination with 5-fluorouracil (5 FU) can be used to relieve dysphagia in over two-thirds of patients with SCC. Symptoms recur, however, due to recurrent cancer or fibrotic strictures. The most effective chemotherapeutic regimen in advanced esophageal cancer is epirubicin, cisplatin, and continuous infusion of 5 FU. Two-thirds of cases respond with improvement of dysphagia. ... 

Lehmann J, Natarajan A, Denardo GL, et al. Short communication nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells. Cancer Biother Radiopharm 2008 23 265-271. 

Chakraborty M et al. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 2004 64 4328-4337. 

Nearly all the experimental and clinical data to date has been using external beam radiation. Furthermore, animal models are not good surrogates for human hepatic radiation response. Whole liver radiation by external beam causes radiation induced liver disease (RILD) in 5%-10% of patients [8-10]. RILD is a clinical syndrome of anicteric hepatomegaly, ascites, and elevated liver enzymes (especially alkaline phosphatase) which occurs usually from 2 weeks up to 90 days post radiation delivery and can lead to permanent, progressive and/or fatal liver dysfunction [11,12]. 

Because resin microspheres carry less activity (50 Bq/ sphere) compared to glass microspheres, many more are used to deliver an adequate dose tumor. With upwards of 40 million-60 million delivered for a typical 2-GBq activity distributed in both lobes of the liver, many patients can experience temporary embolic side effects (pain, fever, nausea) which are similar but far less intense than is seen in TACE post-embolic symptoms. However, not all hepatic vascular beds can accept the number of microspheres desired from the pre-treatment planning formulae, and thus the delivery of microspheres discontinued prior to completely emptying the volume of microspheres planned. It is not the desire or plan to perform an embolic treatment, rather it is a brachyther-apy procedure and therefore it is recommended that the delivery of microspheres not cause stasis and/or reflux. Optimal implantation of microspheres is for the tumor only to have spheres, and the normal adjacent liver to be free of radiation. Once stasis has occurred, however, the normal liver arteries have also been filled with microspheres and the selectivity and therapeutic benefit to brachytherapy is lost. If the whole lobe or segment is receiving the same dose of radiation (tumor and normal liver) then external beam radiation could have been used instead. Also, many patients are selected for microsphere therapy specifically because an embolic treatment was not felt to be safe or in their best interests. 

Background. Radiation induced hepatitis was first described in the 1960s [8] and results in various degrees of hepatic decompensation. It is a well recognized complication of external beam radiation that encompasses the liver [9] since it involves the irradiation of normal parenchyma beyond that which can be tolerated (35 Gy when exposed to uniform radiation fields). However, it is a rare complication after microsphere treatment since this technique allows the safe delivery of radioactive particles to liver tumors with healthy liver tissue sparing [10]. Doses greater than 70 Gy to liver tumors can be delivered without involving the normal liver tissue [11]. 

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