Radiation Therapy – A technicians overview By: Stephanie Corsi, CVT Senior Radiation nurse, PennVet What is ? Radiation therapy uses high-energy radiation or high energy particle () to kill cancer cells and shrink tumors. How does radiation therapy work? Radiation kills cancer cells by damaging their DNA. Cells that are rapidly dividing, like cancer cells, are more susceptible to radiation. The damage is by a high energy photon ejecting a high energy that then reacts with a water molecule to create charged particle, also called free radicals, within the cell that will damage the DNA. Most cells die what is called a “mitotic death”, meaning the cancer cells whose DNA is damaged beyond repair will stop dividing and die. Goal of Radiation: The purpose of radiation is to maximize the likelihood of tumor control while minimizing side-effects to the patient. Radiation may be used alone or in combination with surgery, chemotherapy, or both. “Curative” intent/ definitive therapy: This is given when the prognosis is good. The hope is that treatment will cure a cancer by eliminating a tumor and preventing recurrence. For tumors that are inherently sensitive, relatively small, and localized. Also used to treat residual cancer left behind after surgery, or before surgery to shrink a tumor. Examples: localized lymphomas, certain mast cell tumors, cutaneous squamous cell carcinomas Palliative intent: Not intended to cure, but rather relieve symptoms and reduce suffering. Given when prognosis is poor and quality of life is the primary focus. Used with bulky tumors. Examples: alleviate bone pain associated with osteosarcoma, a tumor pressing on the spine, tumors pressing on the esophagus interfering with breathing/eating, etc. *Radiation & Chemotherapy: Radiation is a localized therapy. Chemotherapy may be used to treat disease outside the radiation field such as lymph nodes and distant micrometastasis. It can also be effective in killing cells that are resistant to radiation. Chemotherapy can also sensitize cells to the effects of radiation such as carboplatin and gemcitabine *Radiation and Surgery: Most common combination in veterinary medicine. Allows for a more conservative, function-sparing surgery. Preoperative/Neoadjuvant: Pros: may be used to shrink the tumor to allow more conservative margins Cons: more difficult to perform surgery on irradiated tissue, increased risk of post-surgical wound complications. Postoperative/Adjuvant: most commonly used. Used to treat residual microscopic, or macroscopic, disease. Pros: fewer tumor cells present which more likely to be actively dividing therefore more susceptible to radiation. Cons: radiation field larger than original tumor to include all tissues that have been surgically manipulated due to possible contamination Types of Radiation: (internal radiation therapy/radiation at a short distance): uses radioactive isotopes Systemic: example: I-131 (radioactive iodine) will bind to thyroid tissue Contact/Plesiotherapy: ex. Sr (strontium) applicators placed directly onto superficial tumors like squamous cell carcinoma of the skin or eye Implants (interstitial/intracavitary): seeds, wires, or beaded ribbons implanted into tissues permanently (low dose-rate) or temporarily (high dose-rate) using hollow catheters placed within the tumor volume, or applicators placed within a body cavity. Rarely used in veterinary medicine. Teletherapy (external beam radiation): Orthovoltage (superficial x-ray): Produces photons in the kilovoltage range (thousands of volts (Kv). These units are obsolete for most human and veterinary uses, although still useful for superficial tumors Megavoltage (deep x-rays): produces high energy photons in the megavoltage range (millions of volts – Mv) that can penetrate deeply into tissues and are also “skin sparing”. Used to treat subcutaneous and deep-seated tumors. Electrons: high energy particles that deliver a high dose of radiation superficially and do not penetrate into underlying tissues External Beam Radiation: A linear accelerator (LinAc) is the most commonly used external radiation therapy device for patients with cancer. The most common in veterinary practices. Modern LinAcs can produce both photons and electrons 3 Dimensional treatment: 3D-CRT (3-dimensional conformal radiation therapy): most common. uses both 3D Imaging (CT/MRI) and sophisticated computer software to deliver radiation to very precisely shaped targeted areas IMRT (Intensity-modulated radiation therapy): Uses multi leaf collimators and multiple gantry angles similar to 3D-CRT but allows for better sparing of normal tissues. IGRT (image-guided radiation therapy): repeated imaging scans are performed during treatment to increase accuracy in targeting the tumor and decreasing dose to normal tissue Stereotactic (Gammaknife, Cyberknife): Extremely accurate image-guided tumor targeting with normal tissue sparing. Typically 3-5 fractions. Best for treating small tumors with well-defined edges. Treatment Planning: Detailed imaging scans are performed to show the location of the patient’s tumor and the surrounding normal tissue. This is done by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound scan, and/or Radiographs. Fractionation: Most types of external-beam radiation therapy are given in once daily fractions. This minimizes damage to normal tissue and increase the likelihood that cancer cells are exposed to radiation at points in the cell cycle when they are most vulnerable to cell damage. The fractionation also allows normal tissues to recover in between each dose. Veterinary Radiation Therapy protocols: Definitive/Full Course/Aggressive(“curative intent”): Most veterinary facilities treat 5 days a week M-F. Smaller doses per fraction, more frequent treatments, and a higher total dose. 15-21 total fractions. Palliative: utilizes few large doses administered 1-2 times weekly for a total of 4-6 fractions. Side Effects: factors include location, size of treatment field, dose given per day, total dose given, concurrent medical conditions (such as Cushing’s or diabetes), and chemotherapy given at same time Acute: occur during treatment. Caused by damage to rapidly dividing normal cells in the area being treated. Includes skin irritation (dermatitis) and hair loss. Causes inflammation (“-itis”) of tissues in the radiation field. (Cystitis, oral mucositis) Most are treated symptomatically and resolve after treatment concludes. Hair may regrow sparse and white in color. The single most important factor in controlling acute side effects is preventing rubbing, scratching, licking or further traumatizing the treatment site. Utilizing Elizabethan collars is very important, as is keeping the area clean and free of crusting. Chronic: occur months to years after treatment ends. Typically cause minimal problems and rarely require treatment. Blood vessels and connective tissues gradually scar over time resulting in stiffness, thickening or thinning of tissues, and a decreased ability to recover from an injury which may result in a non-healing wound. Very small risk of developing a secondary cancer within the radiation tissue. Tumor Types: *Round cell tumors are very sensitive to radiation, carcinomas have a moderate sensitivity, and sarcomas are relatively resistant *Localized tumors are more likely to be curable than those with regional metastasis or tumors that have spread systemically or multicentric tumors. *Well-defined tumors are more amenable to radiation therapy than diffuse disease both due to a constraint on the size of the area that can be safely irradiated and because it is difficult to determine the extent of the area that needs to be treated. *Slowly progressive cancers typically have better long term control than rapidly progressive cancers. Rapidly growing tumors are often most responsive to treatment initially because a large percentage of the tumor cells are actively dividing. Also, tumors tend to regress at a rate similar to their growth rate prior to treatment. Unfortunately tumors that tend to rink rapidly tend to recur or metastasize just as quickly. Tumor Types and Radiation: The What, When, and Why? TYPE: ACANTHOMATOUS EPULIS (ADAMANTINOMA, AMELOBLASTOMA) Histopath: Arises from the periodontal ligament Biology: Locally invasive, not metastatic, can also occur in cats 1st Line of Tx: Surgical excision (maxilectomy or mandibulectomy) When to refer to RT: If surgery is not feasible or incomplete resection Additional Tests: CT Prognosis Following RT: Excellent. 3+ years median survival (even without prior surgery) Local Complications from RT: Dermatitis, mucositis Failure Pattern: local (about 10% of cases). Risk of new tumor at site 3+ years post RT TYPE: CANINE ORAL FIBROSARCOMA Biology: locally invasive, rarely metastatic. Can mimic carnassial tooth abscess 1st Line of Tx: surgical excision When to refer to RT: postoperatively if resection incomplete or if non-surgical Additional Tests: routine bloodwork, chest rads, skull CT Prognosis Following RT: Fair to good Local Complications from RT: dermatitis, mucositis Failure Pattern: local. Rarely LN mets, very rarely pulmonary mets TYPE: BRAIN (primary) Histopath: meningioma, others (including pituitary) Biology: locally invasive 1st Line of Tx: +/- surgery +/- radiation therapy. Consider corticosteroids and anticonvulsants When to refer to RT: at diagnosis or postoperatively Additional Tests: MRI / Brain CT, chest rads, routine bloodwork Prognosis Following RT: Good. Median survival > 1 year in many cases. Many dogs show excellent resolution of clinical signs (e.g. blindness, stupor) within 2 weeks of beginning RT. Performance status prior to therapy has prognostic significance Local Complications from RT: otitis, dermatitis, ocular Failure Pattern: local OTHER: Can also consider stereotactic radiosurgery (SRS) TYPE: ORAL MELANOMA Biology: highly metastatic early in the course of disease 1st Line of Tx: surgery When to refer to RT: postoperatively or post biopsy Additional Tests: routine bloodwork, chest rads, skull CT, LN aspirate Prognosis Following RT: fair, median ~6 months (gross disease) Local Complications from RT: dermatitis, mucositis Failure Pattern: loco regional, widespread metastasis Other: If local disease is not controlled, animal will die of local disease. If local disease controlled, most animals will develop metastasis within 6 months TYPE: SOFT TISSUE SARCOMAS (LOW GRADE), HEMANGIOPERICTYOMA Histopath: fibrosarcoma, nerve sheath tumor, malignant fibrous histocytosis, myxosarcoma, hemangiopericytoma, etc.; i.e. mesenchymal neoplasms of cell types Biology: locally invasive in soft tissue, unlikely to invade bone, rarely metastatic 1st Line of Tx: wide surgical excision, consider amputation if on extremity When to refer to RT: if surgical excision incomplete or recurrent tumor Additional Tests: routine bloodwork, chest rads, rads of lesion. Consider CT/MRI if large primary or multiple recurrences Prognosis Following RT: 50-75% chance 1+ year local control if treating residual disease, hemangiopericytomas may do somewhat better than other histologies Local Complications from RT: skin, rarely underlying bone Failure Pattern: local Other: high grade sarcomas (e.g. feline injection site sarcomas) and undifferentiated sarcomas more likely to metastasize, mainly to lungs but also LN elsewhere TYPE: FELINE GINGIVAL/ORAL SQUAMOUS CELL CARCINOMA Biology: extremely locally aggressive and rapidly growing 1st Line of Tx: if tumor caught early (esp. if rostral or mandibular), surgical excision should be attempted prior to radiation therapy When to refer to RT: at time of diagnosis, ASAP Additional Tests: routine bloodwork, FeLV/FIV, chest rads, CT, LN aspirate Prognosis Following RT: if treating postoperatively, 6-12 months median survival. Adjuvant chemotherapy may improve disease-free interval and survival times Local Complications from RT: osteonecrosis if tumor invading bone. Tongue necrosis if tumor sublingual Failure Pattern: local Other: sublingual SCC very difficult to control locally TYPE: CANINE GINGIVAL SQUAMOUS CELL CARCINOMA Biology: locally invasive, mets to lymph nodes 1st Line of Tx: surgical excision. NSAIDs may be used adjuvantly When to refer to RT: if surgical excision incomplete Additional Tests: routine bloodwork, chest rads, skull CT, LN aspirate Prognosis Following RT: median survival 12-18+ months, rostral better than caudal, smaller better than larger, younger better than older Local Complications from RT: dermatitis, mucositis Failure Pattern: local and regional, rarely distant OTHER: Lingual and nasal planum SCC more likely to be metastatic and difficult to control locally. Tonsillar SCC very aggressive and metastasizes widely even with multimodality therapy TYPE: CANINE NASAL TUMOR Histopath: Usually carcinoma, sometimes chondrosarcoma. Any tissue type is possible Biology: Locally invasive. Rarely metastasizes to the lungs, lymph nodes (submandibular, retropharyngeal), bone Local Complications from RT: dermatitis, mucositis, ocular Failure Pattern: local recurrence, rarely mets