Radiotherapy Uses, complications and management Introduction Radiation - high energy particles & electromagnetic waves emitted by radioactive substances. Classified as ionizing (unstable atoms giving off energy) or nonionizing(radio,microwave,UV). Radiotherapy- therapy using ionizing radiation,to control or kill unwanted cells All forms of ionizing radiation are caused by unstable atoms. In order to reach a stable state, they must release their extra energy or mass in the form of radiation Forms of Radiation Particles: Alpha- big,positively charged. Has two protons and two neutrons. Does not travel far in air,difficult penetration through dead skin,but causes serious damage if ingested. Beta- smaller than alpha but bigger than gamma. Negatively charged,either an electron or a positron, smaller mass,can travel further in air, can penetrate skin a few centimeters NeutronCan travel far in air,lack of a charge- can't ionize an atom directly,but if indirectly absorbed into a stable atom,makes it unstable and more likely to emit off ionizing Forms of radiation Electromagnetic waves: Gamma rays - does not consist of any particles,mass or charge, but energy being emitted from an unstable nucleus.produced by natural decay of radioactive substances.can travel far through air. X-rays - similar to gamma radiation, with the primary difference being that they originate from the electron cloud.are longer-wavelength and lower energy than gamma radiation Pic History -In 1895 Wilhelm Röntgen discovered X-rays while conducting experiments in applying currents to different vacuum tubes and noticing rays penetrating through to react with a barium solution.He took the first photo (of his wife’s hand and skeletal structure) with the new rays -1896 Henri Becquerel’s discovered that uranium salts gave off similar rays -His doctoral student, Marie Curie, named it: radioactivity. -She also discovered additional radioactive elements: thorium, polonium, and radium. She was awarded the Nobel Prize twice, once alongside Henri Becquerel and her husband Pierre in Physics for their work with radioactivity. Indications -curative if cancer is localized to one area of the body(tumor or disease process, draining lymph node beds) -adjuvant therapy- performed in addition to the surgical resection with the goal of treating the resection bed and regional lymph nodes for: -large tumors -recurrent tumors -extracapsular lymph node involvement -positive resection margins. Indications -induction therapy- Large tumors may be treated preoperatively with radiation therapy to reduce the tumor size and difficulty of surgery -prevention of recurrence after surgery to remove a primary malignant tumor (eg. early stages of breast cancer). -synergistically with chemotherapy How is radiation measured? By the energy absorbed from a radiation source per unit mass of tissue. The current unit of measure for therapeutic radiation is the Gray (Gy). The Gray is defined as the absorption of 1 J of ionizing radiation by 1 kg of tissue. Becquerel’s (Bq) - Becquerel is the SI unit for radioactivity. One Bq equals one decay per second Curie (Ci)- (1 Ci equals 370,000,000,000 decays per second) named after Marie and Pierre Curie. Widely used. Dosing type of tumor area of treatment goal of treatment -curative treatment usually ranges from 69 to 80 Gy. -adjuvant treatments within 40 to 60 Gy The total treatment is usually divided/fractionated over several sessions. This allows the non-diseased, tissue that surrounds the tumor, to recover better than giving one large dose Irradiation vs Contamination The two main forms of radiation exposure are: -irradiation - radiation waves that pass directly through the body. Is a local therapy applied to a specific body site -contamination - in contact with and retention of radioactive material(industrial accident)- either fixed or removable. rare. Radiation vs Surgery: Advantages: local treatment of disease preservation of surrounding uninvolved structures Disadvantages: length of treatment. Cost Availability of service. Access to facilities and equipment Additive and chronic effects of radiation therapy Delivery of radiotherapy Via external or internal routes External- most commonly used is external beam radiotherapy. A variety of low energy radiation beams can be delivered in this manner, and allows for daily fractionated delivery of radiation over a several week course. Can be given preoperatively, intraoperatively, or postoperatively. Internal- Delivery of radiation from within the patient's body is termed brachytherapy. allows for continual treatment of the tumor with radiation over a course that usually lasts several days. Delivery of radiotherapy advantages of internal radiotherapy : decreased treatment time greater ability to spare uninvolved local tissues Also for patients who have been previously irradiated and are no longer candidates for external beam therapy - having already reached the maximum dose commonly used for the treatment of pelvic cancers such as cervix or prostate, adjunctive therapy for soft tissue tumors Radiation Damage Interaction of radiation with water molecules within the cell creates free radicals that cause direct cellular damage DNA exposure to radiation results in two different modes of cell death: mitotic (clonogenic) cell death and apoptosis. Vessels- constrictive microangiopathic changes to small-and medium-sized vessels + inhibition of fibroblast function, increased risk of anastomotic failure. Early effects Early effects-first few weeks following therapy. usually self-limiting. Result from damage to rapidly proliferating tissues, such as the mucosa and skin. Erythema and skin hyperpigmentation Dry desquamation -low to moderate doses of radiation, moist desquamation- higher doses, stasis and occlusion of small vessels- significant when planning pedicled/free flaps inhibition of Fibroblast proliferation Late effects Late/chronic radiation effects- anytime from weeks to years. can be permanent tissue fibrosis. telangiectasias delayed wound healing. lymphedema (as the result of cutaneous lymphatic obstruction) ulceration, infection, alopecia, malignant transformation, mammary hypoplasia, xerostomia, osteoradionecrosis, endarteritis. General principles of treating irradiated wounds Pre radiation: Planning preoperatively :This is often seen in the breast mastectomy and immediate recon patient -requires potential postoperative radiation Post radiation: recurrent or new tumor, or a radiated wound not amenable to primary closure, +-exposure of vital structures -requires resection followed by reconstruction. Intraoperative radiation therapy: occasionally used in the treatment of sarcomas, pelvic tumors, and other malignancies. Apply the reconstructive ladder- a primary layered closure can be attempted if possible General principles of treating irradiated wounds In a wound with late radiation changes: Rule out the presence of a recurrent or new tumor : radiographs, CT scans, MRI’s and histology If tumor is present- surgical resection + reconstruction of the defect -If tumor is not present- removal of all nonviable irradiated tissues, may require multiple debridements -Primary closure or skin grafting ? poor vascularity and fibrosis- fail -muscle flaps transposed? Poor vascularity -poor healing -Larger defect ? Principles of Reconstruction -well vascularized nonirradiated soft tissue flap. -flap must be approximated with well-vascularized tissue -Flap planning -choice? healing +preservation of function -irradiated muscle- Risk of partial or complete muscle necrosis. -irradiated pedicle- higher complication rate -use nonirradiated muscle flap or the greater omentum -If these are not available- free tissue transfer -evaluate the tissue surrounding the defect. Skin -non melanoma skin cancers can be treated with irradiation with a 90% cure rate -but prolonged treatment +access? -complications: fibrosis, ulceration, ectropion, osteitis,chondritis uses: -poor surgical candidates -post op for positive cutaneous margins or perineural invasion -post op keloids and hypertrophic scars- fibroblast inhibition Extremities -Goals: Tumor control - usually sarcomas Limb salvage Preservation of function- neurotized muscle recon Coverage of all vital structures- role of reconstructive ladder? -Multidisciplinary- oncologists, vascular, orthopedic( osseus defects:prosthesis,arthroplasty,bone grafts) ,plastics -Surgery+intra/post op radiotherapy -Internal/external radiotherapy - if radiation given preop: internal or lower dose external Breast Ease of recon after radiotherapy depends on: -Use of autologous or prosthetic materials: Delayed wound healing Implant exposure Capsular contractures -patient group Breast Patient group: 1-is undergoing mastectomy and needs postoperative radiation,because of tumor size or nodal involvement 2-received radiation therapy to the breast and now needs recon: well vascularized tissue via autogenous reconstruction > prosthetic implants alone Transverse Rectus Abdominis Myocutaneous (TRAM) flap or a latissimus dorsi muscle flap with an expander/implant Breast Increased incedence of TRAM flap failure when pedicle has been exposed to irradiation Here, we can minimize complications by: -flap delay -bipedicled TRAM flap -turbocharging the flap (controversial) Or a free tissue transfer using a flap not exposed to radiation Breast -immediate reconstrucion vs delayed reconstruction? -potential need for postoperative irradiation is often uncertain at the time of mastectomy -delayed autologous reconstruction is superior to immediate reconstruction and postoperative radiation of the flap -delay reconstruction until the final decision about postoperative irradiation is made Head and Neck Goals: -wound healing and preservation of function -primary goal: complete healing without infection(dehiscence -vessel rupture&anastomotic leak- life threatening), or intraoral breakdown that may result in fistula formation. -secondary goal : maintenance/restoration of function. -Tertiary goal : cosmetically acceptable appearance. Head and Neck Challenges: -aggressive- often requires surgery + radiotherapy -high recurrence rates -extensive surgery-huge defects, fistula a between the oral cavity and the neck vessels, exposure of vital structures,that require soft tissue and/or osseous reconstruction. -difficult reconstruction especially if previously irradiated site -local and regional flaps have been used traditionally, but gold standard is free tissue transfer Head and Neck Local muscle flaps: Pectoralis major muscle flap -limited by its bulk -difficult arc of rotation -limited reach into the oral region Sternocleidomastoid and platysma -not predictable in the irradiated neck Head and neck Free tissue transfer: -vital structures located in the head and neck region, requires a stable closure. -types: thin fasciocutaneous flap (radial forearm flap) intermediate thickness flap (scapula or parascapular flap), variable thickness flap (anterolateral thigh flap). Muscle flaps (rectus abdominis or latissimus dorsi) can also be used. The greater omentum is excellent as a "carrier" for bone and skin grafts but offers no structural strength. Head and Neck Vessels: Abundant large caliber vessels in head and neck- but radiated? Although the irradiated vessels may be adequate for use, difficult dissection due to: inflammation,fibrosis,thickening of the tissue planes and absence of standard anatomic landmarks Preoperative : Plan A and plan B, assess vessels preop,use of contra lateral vessels Head and Neck Osteoradionecrosis of the mandible or maxilla: -requires resection/debridement of affected tissue followed by osseous reconstruction. -The affected regions may be categorized into thirds: lower third -mandible and neck region- fibula flap to deliver well-vascularized nonirradiated tissue to the wound bed, prevents formation of chronic non-healing wounds + draining sinus tracts middle third -maxilla and the orbit-primary vascularized bone grafts upper third -skull base and cranium- skull base must be separated from the oronasal cavity to prevent infection and csf leaks- composite rejections- free tissue transfers-but difficult especially if previously irradiated site Pic Chest Indications for radiotherapy to the chest wall: -treatment of lymphomas -large chest wall or pulmonary tumors -recurrent malignancies after previous resections Difficult to manage complications-houses vital structures Multidisciplinary- cardiothoracics(chest wall recon,aero digestive tract or great vessel injury) Chest Complications: radiation ulcers, infected wounds, persistent or recurrent tumors, cardiac and pulmonary disorders Often critically ill and require prolonged ICU stays Chronic sinus tracts -sternal wires, retained suture, or persistent infected cartilage. Multiple debridements- partial or full thickness defect? Chest Often full thickness defect: -Requires chest wall recon with Prosthetic material eg Prolene mesh -To retain intra thoracic negative pressure Followed by flap coverage: one or both of the pectoralis major, latissimus dorsi,rectus abdominis greater omentum :advantages are its large surface area(covers large and mounds into irregular defects) and excellent vascularity. Perineum Gynecologic malignancies/ anal and peri anal malignancies Challenges: -extensive perineal resections +radiation therapy resulting in perineal wounds not amenable to primary closure -female: vaginal reconstruction+pelvic defect -musculocutaneous,pedicled rectus abdominis,flap of choice.other options,thigh muscles (rectus femoris and gracilis) and fasciocutaneous flaps (anterolateral thigh flap) VVF- greater omentum -male :pelvic defect-delayed perineal wound healing , evisceration and adhesions deep in the pelvis - musculocutaneous flap Fat Grafting -Treatment of radiation damage -adipose-derived stem cells present within the stromal vascular fraction of the fat graft -decreased inflammation and fibrosis Conclusion Radiotherapy has many benefits But beware of late changes following irradiation -reconstructive challenges Different locations offer different problems- be cognizant of these. Always have a plan B But principles remain the same:Establish a diagnosis, if tumor present perform the appropriate workup. Thoroughly debride the radiated wound of all nonviable tissue and foreign bodies Reconstruct osseous defects with vascularized bone Reconstruct soft tissue defects with well-vascularized, nonirradiated soft tissue All neurovascular bundles, bone, tendon, and prosthetic material must be covered with healthy soft tissue. In the case of pedicled flaps, it is better to base a flap on a nonirradiated pedicle, and in the case of free tissue transfer, it is best to use nonirradiated recipient vessels. References 1-Grab and Smith’s Plastic Surgery 7th Edition - Charles H. Thorn 2-www.cancerresearch.uk.org 3-www.elsevier.com/radiotherapyjournals
