Cancer cell lung mesothelioma small

This articles reviews the indications, techniques, and results of brachytherapy in the treatment of non-small cell lung cancer (NSCLC) and selected chest neoplasms. Various isotopes and techniques are used to place radioactive sources directly into a tumor, tumor bed, or the chest. Brachytherapy techniques can be tailored to the clinical situation and can be in the form or permanent interstitial volume or planar implants (radioactive sources permanently imbedded into the tumor or tumor bed) or in the form of temporary interstitial or endoluminal implants (where radioactive sources irradiate a tumor bed over a certain length of time and then are removed). These treatments can be delivered over a short interval (high-dose are [HDR]) or over a more protracted time (low-dose rate). HDR treatments can be used intraoperatively to deliver a large dose of radiation to a determined target area with selective sparing of surrounding normal structures. Different methods of delivering HDR intraoperative radiation are under investigation. Most reports on brachytherapy for chest malignancies are retrospective and come from a few single institutions. Most of the published data relate to the treatment of NSCLC, out other intrathoracic malignancies, such as malignant pleural mesothelioma and malignant thymoma, have been treated with brachytherapy. To our knowledge, no major randomized trials accurately assess or confirm these retrospective studies yet, complicating the interpretation of these results. Nevertheless, brachytherapy is of value in selected situations and offers the clinician and the patient an innovative method of delivering conformal highdose radiation to a defined target with preferential sparing of normal surrounding structures. With continued innovations in the development of radioactive isotopes, computerized treatment planning and targeting, and source delivery, brachytherapy should continue to offer an attractive alternative and complement to conventional treatment approaches, and may offer patients improved local control and survival.

Brachytherapy -- the placement of interstitial or intracavitary radioactive sources into a desired target to facilitate the safe delivery of high radiation doses to tumors, with selective sparing of normal surrounding tissue -- represents a novel approach to the limits of the therapeutic ratio for selected tumors:[1]

Total dose of radiation required to eradicate tumor/ Tolerance dose of surrounding normal tissue

When the therapeutic ratio required to eliminate a tumor exceeds the tolerance of clinical normal structures, conventional external-beam radiation therapy (EBRT) rarely achieves local control without undue morbidity. Non-small cell lung cancer (NSCLC) and other selected chest neoplasms thus represent a difficult challenge. Dose-limiting vital structures, such as normal lung, heart, and spinal cord, limits the dose that can be delivered with conventional means. Brachytherapy has been explored as an alternative treatment modality to manage selected tumors arising in or metastasizing to the chest.

Brachytherapy for NSCLC has historical roots dating back approximately 60 years, when Graham and Singer[2] first described seven cases of interstitial bronchial stump implantation with radon 222 ([sup.222.Rn]) radioactive seeds after thoracotomy and pneumonectomy. Shortly thereafter, Henschke[3] introduced modern afterloading techniques with gold 198 and iridium 192 ([sup.192.Ir]), which led to a rapid increase in the use of these isotopes and techniques in the United States. Despite these technologic advances, this specialized area of radiation oncology failed to gain widespread use for several reasons. Many early isotopes available for implantation exposed physicians and hospital personnel to unacceptable levels of radiation. Isotopes were not always readily available. Additionally, both interstitial and intraluminal brachytherapy require a substantial level of surgical skill to be administered safely and efficiently.

The use of brachytherapy in the treatment of NSCLC as recently enjoyed renewed enthusiasm as a result of the introduction of newer isotopes (ie, iodine 125 [[sup.125.I]] and palladium 103 [[sup.103.Pd]]), improved treatment planning, increasing numbers of radiation oncologists who have been trained to perform these procedures, and the introduction of computerized technology and software to optimize treatment planning.[4]

A fundamental goal of radiotherapy is to maximally deliver dose to tumor while minimizing dose to surrounding normal tissue. Brachytherapy represents one of the best means to accomplish this goal. Its several methods depend on the stage and location of the tumor, as well as the performance status and pulmonary function of the patient and previous radiotherapeutic intervention. Radioactive isotopes can be placed interstitially in a permanent setting or as a temporary afterloading implant. They can also be used to deliver localized radiation for intraluminal tumors involving the trachea and bronchial tree. This article describes the indications, techniques, and results achieved with brachytherapy for the treatment of NSCLC and other selected neoplasms arising in the chest.

Interstitial Permanent Volume or Planar Implantation

The optimal technique of intraoperative implantation and the selection of radioactive sources depend on the location of the tumor, the amount of residual gross disease, and the biological behavior of the tumor. When residual tumor volume exceeds 1 cm, a permanent volume implant is usually required. The area to be implanted is determined preoperatively by the surgeon and the radiation oncologist, then reevaluated intraoperatively. The dimensions are recorded. A volume nomogram is applied to integrate information obtained from the average dimension of the area to be implanted and the available isotopic seed strength, to determine the number of seeds and spacing of both seeds and needless (volume implant) required to deliver a minimum peripheral dose (MPD) to the tumor.

[sup.125.I] and [sup.103.Pd] are the two most common sources employed for permanent volume implant. The MPDs for [sup.125.I] and [sup.103.Pd] are typically in the ranges of 14,000 to 16,000 cGy and 10,000 to 13,000 cGy, respectively. Although the energies of [sup.125.I] and [sup.103.Pd] are similar (0.028 MeV and 0.021 MeV), their half-lives differ significantly (60 days and 17 days, respectively), resulting in different dose rates (7 to 8 cGy/h and 20 cGy/h).[5] This theoretically implies a potential biological advantage to selecting [sup.103.Pd] (short half-life, rapid dose rate) in the setting of rapidly growing tumors.[6] Once the dosimetry is planned, hollow metallic trochars are inserted into the tumor. Radioactive sources are implanted with an applicator (Mick Applicator; Mick Industries; New York). Postoperatively, localization radiographs determine the delivered MPD, base on the geometry of the implanted seeds.

For either close or positive margins or minimal residual disease ([is less than] 1 cm), a permanent planar implant is performed. Less often, a permanent planar implant is used for early lesions. It is also indicated when tumor is partially resected, either because of proximity to critical vasculature or crossing fissure lines into adjacent lobes. The length and height of the visible target are defined and a planar nomogram is used to determine the number of seeds and spacing required to deliver a MPD of 14,000 to 16,000 cGy (for [sup.125.I]) or 11,000 to 13,000 cGy (for [sup.103.Pd]). The [sup.125.I] or [sup.103.Pd] seeds imbedded in polyglactin (Vicryl) sutures are then either sewn onto a premeasured Dexon or polyglactin mesh and then implanted onto the target, or directly sutured onto the target area. A similar technique employing [sup.125.I] embedded into an absorbable gelatin sponge (Gelfoam) plaque has also been described.[7] These differing approaches are used based on the proximity of the target area to critical structures that can or cannot be directly sutured. After implantation, localization radiographs determine the actual dose delivered to the target area as outlined by the radiation oncologist. Once the implant is performed and the incision is sutured, the dose cannot be adjusted, presenting a potential disadvantage.

Interstitial Temporary Implantation

Temporary interstitial implants are used to treat tumors arising or metastasizing to the anterior mediastinum, chest wall, or paraspinal region. Typically, after gross total or incomplete resection, the tumor bed is implanted with either low-dose rate (LDR) or remote afterloading highdose rate (HDR) [sup.192.IR] or [sup.125.I]. Relatively easy access via a percutaneous approach often dictates the use of this technique, either as a single treatment modality or in combination with EBRT.