To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.
Nat Rev Clin Oncol. 2011 Jul 26.
CLINICAL IMPLICATIONS OF RADIO-NECROSIS TO THE HEAD AND NECK SURGEON.
Radiation necrosis is one of the most serious complications in the treatment of malignancies of the head and neck. As radiotherapy becomes more frequently used as a primary modality and in combination with chemotherapy and surgery, the head and neck surgeon needs to be able to prevent and recognize the often subtle signs and symptoms of radiation necrosis. The symptoms of necrosis can mimic the recurrence of cancer, which presents a diagnostic dilemma, because aggressive surgical biopsy may worsen necrosis and contribute to the formation of a fistula. This review provides a brief discussion of the diagnostic and treatment options for osteoradionecrosis and chondroradionecrosis in the head and neck.
Curr Opin Otolaryngol Head Neck Surg. 2003 Apr;11(2):103-6.
INCREASED RISK OF ISCHEMIC STROKE AFTER RADIOTHERAPY ON THE NECK IN PATIENTS YOUNGER THAN 60 YEARS.
PURPOSE: To estimate the risk of ischemic stroke in patients irradiated for head and neck tumors. PATIENTS AND METHODS: The incidence of ischemic stroke was determined in 367 patients with head and neck tumors (162 larynx carcinomas, 114 pleomorphic adenomas, and 91 parotid carcinomas) who had been treated with local radiotherapy (RT) at an age younger than 60 years. Relative risk (RR) of ischemic stroke was determined by comparison with population rates from a stroke-incidence register, adjusted for sex and age. Other risk factors for stroke (hypertension, smoking, hypercholesterolemia, diabetes mellitus [DM]) were registered. The median follow-up time after RT was 7.7 years (3,011 person-years of follow-up). RESULTS: Fourteen cases of stroke occurred (expected, 2.5; RR, 5.6; 95% confidence interval [CI], 3.1 to 9.4): eight in patients with laryngeal carcinoma (expected,1.56; RR, 5.1; 95% CI, 2.2 to 10.1), four in pleomorphic adenoma patients (expected, 0.71; RR, 5.7; 95% CI, 1.5 to 14.5), and two in parotid carcinoma patients (expected, 0.24; RR, 8.5, 95% CI, 1.0 to 30.6). Five of six strokes in patients irradiated for a parotid tumor occurred at the ipsilateral side. Analysis of other risk factors for cerebrovascular disease showed hypertension and DM to cause an increase of the RR after RT. After more than 10 years' follow-up, the RR was 10.1 (95% CI, 4.4 to 20.0). The 15-year cumulative risk of stroke after RT on the neck was 12.0% (95% CI, 6.5% to 21.4%). CONCLUSION: This is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patients.
J Clin Oncol. 2002 Jan 1;20(1):282-8.
CORONARY ARTERY DISEASE MORTALITY IN PATIENTS TREATED FOR HODGKIN'S DISEASE.
The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0.97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease.
Cancer. 1992 Mar 1;69(5):1241-7.
LONG-TERM COMPLICATIONS ASSOCIATED WITH BREAST-CONSERVATION SURGERY AND RADIOTHERAPY.
BACKGROUND: Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications. METHODS: We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 (an era in which standard radiation dosages were used) with follow-up for at least 1 year. Patients were prospectively monitored for treatment-related complications. Median follow-up time was 89 months. RESULTS: A total of 294 patients met the selection criteria. Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients, breast skin fibrosis in 12, decreased range of motion in 4, pneumonitis in 2, neuropathy in 2, fat necrosis in 1, and rib fracture in 1. Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone. Arm edema occurred in 18% of patients who underwent surgery plus irradiation of the lymph nodes and 10% who underwent surgery without nodal irradiation. CONCLUSIONS: Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9% of patients. Half of these complications were attributable to axillary dissection, it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy. Breast-conservation surgery and radiotherapy is associated with grade 2 or greater complications in only 9.9% of patients. Nearly half of these complications are attributable to axillary dissection.
Ann Surg Oncol. 2002 Jul;9(6):543-9.
RISK OF LYMPHOEDEMA FOLLOWING THE TREATMENT OF BREAST CANCER.
The incidence of lymphoedema was studied in 200 patients following a variety of treatments for operable breast cancer. Lymphoedema was assessed in two ways: subjective (patient plus observer impression) and objective (physical measurement). Arm volume measurement 15 cm above the lateral epicondyle was the most accurate method of assessing differences in size of the operated and normal arm. Arm circumference measurements were inaccurate. Subjective lymphoedema was present in 14% cent whereas objective lymphoedema (a difference in limb volume greater than 200 ml) was present in 25.5%. Independent risk factors contributing towards the development of subjective late lymphoedema were the extent of axillary surgery (P less than 0.05), axillary radiotherapy (P less than 0.001) and pathological nodal status (P less than 0.10). The risk of developing late lymphoedema was unrelated to age, menopausal status, handedness, early lymphoedema, surgical and radiotherapeutic complications, total dose of radiation, time interval since presentation, drug therapy, surgery to the breast, radiotherapy to the breast and tumour T stage. The incidence of subjective late lymphoedema was similar after axillary radiotherapy alone (8.3%), axillary sampling plus radiotherapy (9.1%) and axillary clearance alone (7.4%). The incidence after axillary clearance plus radiotherapy was significantly greater (38.3%, P less than 0.001). Axillary radiotherapy should be avoided in patients who have had a total axillary clearance.
Br J Surg. 1986 Jul;73(7):580-4.
RADIATION-INDUCED CORONARY ARTERY DISEASE.
Radiation-induced heart disease must be considered in any patient with cardiac symptomatology who had prior mediastinal irradiation. Radiation can affect all the structures in the heart, including the pericardium, the myocardium, the valves and the conduction system. In addition to these pathologies, coronary artery disease following mediastinal radiotherapy is the most actual cardiac pathology as it may cause cardiac emergencies requiring interventional cardiological or surgical interventions. Case A 36-year-old man was admitted to the clinic with unstable angina pectoris of one month duration. The patient had no coronary artery disease risk factor. The history of the patient revealed that he had mediastinal radiotherapy due to Hodgkin's disease at 10-year of age. Coronary arteriography showed total occlusion of the left anterior descending artery and 70% stenosis of the proximal right coronary artery. Both arteries are dilated with placement of two stents. Control coronary arteriography at the end of the first year showed patency of both stents and the patient is free of symptoms. Previous radiotherapy to the mediastinum should be considered as a risk factor for the development of premature coronary artery disease. Percutaneous transluminal coronary angioplasty with stent placement or surgical revascularization are the preferred methods of treatment. Preoperative assessment of internal thoracic arteries should be considered prior to surgery. As the radiation therapy is currently the standard treatment for a number of mediastinal malignancies, routine screening of these patients and optimal cardiac prevention during radiotherapy are the only ways to minimize the incidence of radiation-induced heart disease.
Z Kardiol. 2003 Aug;92(8):682-5.
COMPLICATIONS OF AXILLARY LYMPH NODE DISSECTION FOR CARCINOMA OF THE BREAST: A REPORT BASED ON A PATIENT SURVEY.
BACKGROUND: Axillary lymph node dissection is commonly performed as part of the primary management of breast carcinoma. Its value in patient management, however, has recently been questioned. Few studies exist that document long term complications. METHODS: Four hundred thirty-two patients with Stage I or II breast carcinoma who were free of recurrence 2-5 years after surgery were identified. A cross-sectional survey was conducted to determine the prevalence of long term symptoms and complications as perceived by the patient, and patient and treatment factors that may have predicted complications were determined. Three hundred thirty of the 432 (76%) completed a mailed, self-administered questionnaire. In addition, the medical records of the 330 patients were reviewed. Patient and treatment factors were analyzed with logistic regression. RESULTS: Numbness was reported by 35% of patients at the time of the survey. Pain was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%. Eight percent reported episodes of infection or inflammation at some point since the diagnosis of breast carcinoma. The majority of symptoms were mild and interfered minimally with daily activities. Younger age (P=0.001) was associated with more frequent reporting of pain. Numbness was more common in younger patients (P=0.004) as well as in those with a history of smoking (P=0.012). There was a positive association of limitation of arm motion with adjuvant tamoxifen therapy (P=0.016). Arm swelling was associated with both younger age (P=0.004) and greater body surface area (P=0.008). Radiation therapy was associated with a higher frequency of infection or inflammation in the arm and/or breast (P=0.001). CONCLUSIONS: Mild symptoms, especially pain and numbness, are common 2-5 years after axillary lymph node dissection. The frequency of inflammation or infection in patients treated with radiation to the breast or chest wall after an axillary lymph node dissection may be greater than previously appreciated. Severe complications or symptoms that have a major impact on daily activities are uncommon. These findings should help health care providers and their patients with breast carcinoma weigh the pros and cons of axillary lymph node dissection.
Cancer. 1998 Oct 1; 83(7):1362-8.
ARE DEATHS WITHIN 1 MONTH OF CANCER-DIRECTED SURGERY ATTRIBUTED TO CANCER?
BACKGROUND: Cancer mortality should include not only deaths from cancer but also deaths from cancer treatment. By convention, deaths within 30 days of a surgical procedure are considered treatment-related deaths in the calculation of operative mortality-that is, the chance of dying from surgery. How cause of death is attributed in patients who die within 1 month of cancer-directed surgery is unknown. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program data from 1994 through 1998 were used to examine the cause of death in patients diagnosed with one of 19 common solid tumors who had died within 1 month of diagnosis and had also received cancer-directed surgery. We determined the proportion of deaths not attributed to the cancer and the magnitude of the undercount in cancer-specific mortality. RESULTS: Among 4,135 patients with only one cancer who died within 1 month of diagnosis and cancer-directed surgery, the proportion of deaths not attributed to the coded cancer was 41% (1,714/4,135), ranging from 13% (1/8) for cervical cancer to 81% (13/16) for laryngeal cancer. Selected intermediate values include 25% (14/56) for esophageal cancer, 34% (177/525) for lung cancer, 42% (719/1695) for colorectal cancer, 59% (110/186) for breast cancer, and 75% (80/106) for prostate cancer. Restricting the analysis to deaths following specific major procedures (e.g., esophagectomy, pneumonectomy, colectomy) had little effect on the findings. If all deaths within 1 month of cancer-directed surgery were attributed to cancer, cancer mortality would rise about 1%. CONCLUSION: Some deaths that are conventionally attributed to surgery are not being attributed to the cancer for which the surgery was performed. Although the estimated effect of this misclassification on overall cancer mortality is modest, it may be indicative of more widespread confusion about how to code treatment-related deaths of patients with cancer.
J Natl Cancer Inst. 2002 Jul 17;94(14):1066-70.
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