reconstruction. Patients with multiple high-risk comorbid factors or frailty may be good candidates for

definitive radiation in order to avoid general anesthesia or prolonged inpatient recovery.

Radiation Therapy Delivery

The systems and technology used to generate and focus photons and electrons toward a target field can

vary based on the requirements of each clinical scenario. Over the past several decades, techniques have

advanced to generate a more focused beam of photons with increased delivery to target tissues and

reduced collateral injury to normal tissue.

External beam radiation therapy is the most commonly employed therapeutic radiation strategy.

Multiple angles of approach are used to deliver multiple beams of radiation to a target region.

Modifiable factors with this approach include the angles of beam delivery, the shape of the beam, and

the intensity of each beam. The radiation oncologist can adjust these factors to maximize the radiation

dose focused on the target tissue while minimizing the effect on nearby, associated radiosensitive

tissues. Patients undergo simulation as an early step in treatment planning. Contemporary simulation is

typically performed with CT scan guidance. During this process, a patient undergoes a CT scan during

which the radiation oncologist identifies the intended isocenter within target area. Using an integrated

laser system to align the isocenter with sites on the patient surface, the radiation oncologist places

tattoos to ensure reproducible, accurate beam alignment for future treatments. Patients typically

undergo radiation treatment for 5 days a week for up to 6 weeks. Intensity modulated radiation therapy

(IMRT) is an enhanced version of external beam therapy. IMRT uses mechanical devices or multiple

beam integration to adjust the intensity within each beam in order to account for irregular patient

surfaces or sensitive structures near the treatment region. By modifying the intensity within the beam, a

more homogeneous dose distribution can be achieved within the target area.

Stereotactic body radiation therapy (SBRT) is a more specialized delivery system used for patients with

brain tumors, lung cancer, and liver tumors. The applications of this technique are rapidly evolving as

the expertise within the radiation oncology community grows. SBRT relies on precise motion control,

high degrees of quality insurance, hypofractionation (commonly 1 to 5 treatments), and a relatively

high dose per fraction to deliver a potentially ablative dose to the target area. Whereas conventional

external beam radiotherapy may deliver a dose of 45 to 60 Gy over a course of 25 fractions

(approximately 2 Gy per fraction), SBRT delivers 7 to 15 Gy per fraction with a lower number of total

fractions. This technique has the potential to be a more definitive therapeutic option than conventional

radiotherapy in light of the ablative intent of the treatment.

The use of radioactive implants, or brachytherapy, is common in the treatment of prostate and

gynecologic cancers. Radioactive seeds can be placed either directly into the tumor (interstitial therapy)

or within catheter-containing applicators placed in the vicinity of the tumor bed (intracavitary therapy).

Intracavitary therapy has been developed as a potential adjuvant therapy for patients following

resection of soft tissue sarcoma or partial mastectomy in the setting of breast conservation therapy.163

The use of intracavitary therapy in these clinical settings is being explored but has certainly not

achieved widespread acceptance.

In addition to intraoperative placement of radiation delivery applicators following resection, surgeons

have assisted with radiation delivery through the use of intraoperative radiation therapy. In select

environments where a specialized intraoperative irradiator is available, radiation is given directly to the

tumor bed where incomplete marginal resection has been performed. The radiation is delivered in a

single fraction of 10 to 15 Gy in combination with more traditional perioperative external beam

radiation. The most common clinical applications for this technique have been in the treatment of pelvic

and retroperitoneal tumors such as recurrent rectal cancer and retroperitoneal sarcoma.

The Role of Chemotherapy in Cancer Management

The use of chemotherapy as a modality in the treatment of cancer is almost universal and its efficacy is

based on systemic treatment of primary and metastatic cancer. Unlike surgical resection or radiation

therapy, the goal of chemotherapy is not necessarily localized or locoregional but systemic cancer

treatment.

The setting in which chemotherapy is given can be defined as neoadjuvant, conversion, adjuvant, or

palliative, dependent on the goals of the planned treatment course. Neoadjuvant chemotherapy is

administered prior to a planned curative surgical resection. The primary or metastatic tumor is

considered technically resectable at baseline but due to oncologic concerns of aggressive tumor biology

a period of chemotherapy is used. An example of neoadjuvant chemotherapy is in the treatment of

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advanced gastric cancer. The MAGIC trial for resectable gastroesophageal cancer included a treatment

arm where patients with either node positive or locally advanced (by T tumor stage) gastric cancer

were treated with a short course of chemotherapy prior to curative gastrectomy.164 The potential

benefits of neoadjuvant chemotherapy is to treat micrometastatic disease not seen on preoperative

imaging, improve tumor-related symptoms, to allow for a period of time where metastatic disease can

present precluding unwarranted surgical resection, and an in vivo method of determining tumor

chemosensitivity. Conversion chemotherapy is also administered prior to surgical resection but the

baseline tumor is considered unresectable, typically due to technical reasons, unlike in the neoadjuvant

setting. An example of conversion chemotherapy is the administration of systemic chemotherapy to

patients with metastatic colorectal liver metastases where upfront surgical resection is precluding by a

sufficient future liver remnant.165,166 The goal of conversion chemotherapy is to downsize the baseline

tumor allowing a safe curative resection. Adjuvant chemotherapy is administered in the postoperative

setting after the primary or metastatic tumor is surgically resected. This is perhaps the most common

setting of chemotherapy administration. Palliative chemotherapy is the setting defined as unresectable

primary or metastatic cancer where the goal of chemotherapy is prolongation of life and not necessarily

conversion to a curative resection.

The choice of systemic chemotherapy regimens is oftentimes tumor specific and is based on

demonstrated efficacy in large phase III randomized controlled clinical trials. Table 14-12 lists the most

commonly administered chemotherapy regimens, the presumed mechanism of action, and the applicable

cancers treated.

The increasing knowledge of cancer genetics and biology has generated potential new targets for

systemic therapeutic regimens ushering in potential individualized cancer treatments. The best example

of a genetic abnormality with a systemic therapy specific for a molecular target is the BCR-ABL

chromosomal translocation seen in patients with chronic myelogenous leukemia (CML).167 The BCR-ABL

fusion protein is a dysregulated tyrosine kinase that has a causal role in the development of CML and

serves as the target for a new class of molecular inhibitors, tyrosine kinase inhibitors. The use of

imatinib mesylate in CML has served as a prototype for the development of molecular target agents in

other cancers, including gastrointestinal stromal tumor.168 Unfortunately, most tumors, including the

most common types, are genetically complex and do not offer a single target that serves as the critical

inhibition point for cancer cell death.

Lack of single, molecular targets has led to the development of molecular targeted agents aimed at

inhibition of pathways. An example of such a druggable pathway is the VEGF and its receptor (VEGFR).

The VEGF pathway is an important regulator of physiologic and pathologic angiogenesis and is thought

to promote tumor cell growth through increased vascular permeability, migration, differentiation of

endothelial cells, and mobilization of bone marrow–derived endothelial cell precursors.169

Overexpression of VEGF and/or VEGFR occurs in most common types of cancers and is associated with

worse tumor presentation and outcome measures.170–172 In 2004, the Federal Drug Administration

approved bevacizumab, a humanized murine monoclonal antibody directed against VEGF, for the

treatment of metastatic colorectal carcinoma.173 Subsequent approval of sunitinib, sorafenib, and

axitinib, three molecular targeted agents with activity against tyrosine kinase in addition to VEGF for

renal cell carcinoma and HCC has established targeting pathways as a viable target for cancer

therapeutics.174–177

Table 14-12 Common Systemic Therapeutic Agents for the Treatment of Cancer

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Staging (Traditional and Genetic)

Cancer staging is the process of determining the cancer burden within the body and the location.

Staging describes the severity of an individual’s cancer based on the magnitude of the original or

primary tumor as well as on the extent of cancer spread via metastases. Understanding and properly

staging cancer is important as it provides a common language for communication among providers and

patients, is a prognostic marker of outcome, allows appropriate treatment decisions, and stratifies

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