2 Multi‐modal Therapy

       Tania A. Banks, Christine Mullin, and Craig A. Clifford

Introduction

      A multi‐modal approach incorporates a combination of some or all of surgery, radiation, and chemotherapy as the backbone of therapy options, and encompasses less common treatments such as gene therapy, photodynamic therapy (PDT), cryotherapy, and immunotherapy on a case‐by‐case basis. Treatment protocols which involve multi‐modal therapy inherently require a planned and coordinated approach from the outset involving the surgeon, the radiation oncologist, the medical oncologist, and the Owner working together to achieve the best outcome. All specialists must know the animal’s status and special situation as well knowing the owner. This way nothing is “lost in translation” and confidence is maintained, resulting in a strong sense of trust. The surgeon, who operates on an animal with a solid tumor, then refers to a radiation oncologist to “mop up” residual disease has likely done the animal a disservice. Upfront surgical and radiation therapy planning minimizes surgical morbidity and minimizes normal tissue radiation injury while maximizing the efficacy of the union of modalities.

Surgery

      Surgery remains the mainstay for treating many types of cancer in pets, and the value of a competent surgical oncologist cannot be understated. The type of surgical mindset, specific knowledge, and technical prowess required is a specialized skill. Such a surgeon appreciates and can deliver what is required to expertly attempt a surgical cure or completely change tack for a palliative or diagnostic approach and employ other modalities synergistically.

Radiation Therapy

Radiation therapy as an addition to the available treatment options allows a greater scope and choice of therapy in many instances. Examples of tumors commonly treated with radiation include certain oral tumors, nasal tumors, brain tumors, mast cell tumors, and soft tissue sarcomas. Radiation can be used with palliative (e.g. to palliate bone pain with primary appendicular osteosarcoma) or curative intent and be used on its own or with surgery. Sources of radiation therapy include megavoltage (>1 million electron volts of photon energy = high energy; maximum dose to tumor rather than skin) and orthovoltage (150–500 kVp = low energy; maximum dose to skin surface) external beam radiation, brachytherapy (interstitial placement of radioactive isotopes), or systemic or cavitary injection of radioisotopes (e.g. iodine131). Megavoltage irradiation has advanced with 3D imaging and planning, multi‐leaf collimators, and custom‐made blocks (Figures 2.1–2.3).

Surgery and Radiation

Radiation can be used post‐operatively, pre‐operatively, or intraoperatively, depending on tumor type and location. For example, radiation can be used post‐operatively (adjuvantly) to treat a solid tumor in a location where wide complete margins cannot be achieved without limb amputation to save the limb. In this scenario, the radiation oncologist should be involved prior to surgery so that he or she can see if this approach is feasible; appreciate the size, fixation, and exact location of mass; plan the radiation field size and shape; determine how to spare normal tissue and include a large enough field; meet the owners; discuss complications, costs, expected outcome; etc. The surgeon’s role in this setting is a delicate, minimal surgery with the intent to preserve blood and oxygen supply to the tissue to increase the effectiveness of radiation. A marginal resection to remove all macroscopic tumor and allow primary closure is performed, and radiation therapy is used with surgery to provide long‐term tumor control or cure. This approach differs greatly from a failed curative‐intent surgery and a poorly healed or open, hypoxic, radiation‐resistant wound and a delayed start to radiation therapy: a situation that is avoided by a team approach and good planning. When adjuvant radiation is planned, the surgeon can help the radiation oncologist by decreasing wound complications such as infection, dehiscence, and seroma formation. Preservation of blood supply, gentle tissue handling, aseptic technique, attention to hemostasis, use of fine, non‐irritating (inert) suture material in minimal amounts, obliteration of dead space in the wound, avoidance of tension, post‐operative rest, and use of bandages are all important. Drains should be avoided if possible, and if they are used, drainage entry and exit holes are included in the radiation field. Hemoclips can be placed in the wound intraoperatively to delineate the boundaries of the excised gross tumor burden to assist the radiation oncologist in planning the radiation field (McEntee 2004, 2008).

Figure 2.1 (a) Standard or conventional linear accelerator. Most of the machines used in veterinary medicine produce electrons of varying energies as well as 6–20 MV photons. (b) Cobalt‐60 machine. This type of radiation‐producing machine relies on a Cobalt‐60 radiation source inside the head of the gantry. The half‐life of Cobalt‐60 is 5.27 years, necessitating replacement when the source decays to a negligible level. These types of machines are decreasing in popularity in veterinary medicine. (c) Linear accelerator with on‐board imaging. These linear accelerators are equipped with a cone‐beam CT in order to image a patient immediately prior to a radiation treatment. This is done in order to accurately localize a tumor in relation to surrounding anatomy and ensure precise dose delivery. These machines are often capable of conventional radiotherapy, intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and electron therapy.

      Photo courtesy of AAPM.org.

      (d) CyberKnife Stereotactic Radiosurgical unit. A CyberKnife is a linear accelerator mounted on a robotic arm. This allows delivery of radiation from thousands of angles around a tumor. KV x‐ray sources are positioned at orthogonal angles above the CyberKnife, which allow for accurate tumor localization with sub‐millimeter accuracy.

      Source: Photo courtesy of Accuray.com.

Figure 2.2 (a) Conventional (i.e. standard) radiation plan for a nasal tumor (outlined in orange). In order to deliver the prescribed dose of radiation to the tumor, the right eye (outlined in blue) needed to be included in the radiation treatment field.

      Source: Image courtesy of Siobhan Haney, DVM, MS, DACVIM (Radiation Oncology); Veterinary Cyberknife Cancer Center, Malvern, PA.

      (b) Stereotactic body radiation therapy (SBRT) plan for a nasal tumor, which demonstrates how the dose can be sculpted to treat the tumor with a high dose of radiation (red areas) and the normal tissues receive a significantly lower dose (blue areas). The graph in the top right corner is a dose volume histogram. The tumor

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