Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities

PURPOSE: To evaluate the clinical outcome of Kimura's disease and to identify the optimal treatment regimen for Kimura's disease. METHODS AND MATERIALS: Between 1984 and 2003, 14 patients with Kimura's disease were treated with radiotherapy (RT) and 9 patients were treated with local excision or systemic steroids. The radiation doses ranged from 20 to 45 Gy. Immunohistochemical studies were performed in 13 cases. RESULTS: At RT completion, a marked response in terms of tumor size was noted in most cases. The median follow-up was 65 months. Local control was obtained in 9 (64.3%) of the 14 in the RT group and in 2 (22.2%) of the 9 in the non-RT group. No secondary malignancies were observed in the RT group. CONCLUSION: These results supports the finding that RT is more effective against Kimura's disease. Simple or immunohistochemical features did not influence the treatment outcome.     

Kimura's disease: a case report and literature review

Kimura's disease, which occurs endemically in the Far East and sporadically in the West, has so far eluded efforts to determine its exact pathogenesis. It presents as solitary or multiple benign swellings of the skin, has a predilection for the periauricular and scalp regions, and often is associated with regional lymphadenopathy. Morphologically, the lesions are characterized by proliferating blood vessels with rich eosinophilic infiltrate. Peripheral blood eosinophilia and raised serum IgE levels are signature features of the condition. The overall prognosis is good. When surgery is not possible, conservative treatment with either corticosteroids or radiation often can produce a favorable response. Complete surgical excision whenever feasible is the preferred treatment despite a high recurrence rate. Based on a recent case of Kimura's disease in a 55-year-old black woman, we discuss the pitfalls in the diagnosis of this chronic inflammatory disorder.     

Desmoid tumors: Local control and patterns of relapse following radiation therapy

Desmoid tumors are benign neoplasms, arising from musculoaponeurotic tissues, which tend to be locally infiltrative, resulting in a high rate of local recurrence following surgical resection. Nineteen patients with desmoid tumors underwent radiation therapy at the University of California, San Francisco, between 1970 and 1980. Fifteen patients were referred with local recurrence following one or more surgical resections. Three patients were referred for initial radiation therapy with unresectable tumors, and one patient received planned postoperative irradiation following subtotal tumor resection. At the time of treatment, 8 patients had nonresectable disease measuring greater than 10 cm. Five patients had residual tumor masses measuring 4 to 6 cm, and six had only microscopic disease following resection. The majority of patients were treated to a tumor dose of 50–55 Gy at 1.6 to 1.8 Gy per fraction. With a median follow-up of 8 years, 13 patients remained free of recurrent disease following radiation therapy. The 5 year relapse free survival was 72% with 10 patients continuing to be free of disease 5 to 11 years following therapy. Local control was not related to the amount of disease present at the time of treatment. Of the 6 patients who developed recurrent disease, only 1 patient had a true in-field recurrence. Four patients recurred at the margin of the radiation field 1 to 5 years following therapy. Of these four patients, 3 were successfully salvaged while 1 died as a result of tumor extension into a major vessel. One patient with an extensive mesenteric mass did not respond to therapy and died 1 month post irradiation. The patient with the in-field recurrence and 1 patient with a marginal recurrence were successfully treated with combination chemotherapy. Moderate dose radiation therapy to desmoid tumors can result in lasting local control when surgical resection is not possible. Post operative radiation can improve the rate of local control for patients with a high risk of recurrence. As desmoid tumors tend to be locally infiltrative, fields must be very generous to prevent marginal recurrence. Systemic chemotherapy offers an alternative to ablative surgery in the event of local failure following radiation therapy.     

Video Material as an Effective Educational Tool to Address Informational and Educational Needs of Cancer Patients Undergoing Radiation Therapy

With increasing rates of cancer patients undergoing radiation therapy, the treatment itself can cause patients significant amounts of anxiety and distress. This can be attributed to the diagnosis of the disease, lack of knowledge of what radiation therapy is, expectations and management of side effects, and the lack of knowledge of supportive care for patients and their families. Providing patients with effective educational tools to meet the informational needs of cancer patients undergoing radiation therapy can empower patients and allow them to participate in treatment decision-making and their own healthcare. This discussion paper will evaluate several studies on the psychological impact of cancer patients undergoing radiation therapy and how video material can effectively meet the informational and educational needs of this patient population group.     

Radiation therapy as an adjunct to primary surgery in early stage breast cancer: biological and clinical rationale.

In spite of the widespread use of adjuvant endocrine and cytotoxic chemotherapy, a substantial proportion of patients with early-stage breast cancer eventually develop a distant disease recurrence. Local control also remains a clinically significant problem in subsets of patients. Whether improved local control through the use of postoperative radiation therapy would prevent distant dissemination has been much debated for several decades. Studies on the long-term outcome of systemically untreated breast cancer patients indicate that breast cancer in many patients is a local disease that can be cured by surgery or radiotherapy. Randomized trials of breast screening have also shown that a delay in effective local treatment is associated with an increased incidence of distant dissemination and death from to the disease. Data from individual randomized trials and overviews of postoperative radiation therapy have indicated that radiation therapy as an adjunct to primary surgery is associated with a decrease in distant dissemination and breast cancer death. This benefit may be translated into a substantial overall survival benefit, provided that the treatment technique avoids long-term cardiac side effects. In many of the older radiation therapy trials, such effects appear to have balanced the benefit in terms of a reduced incidence of distant disease among the patients allocated to radiotherapy.     

Optimising radiation treatment decisions for patients who receive neoadjuvant chemotherapy and mastectomy

Whereas randomised clinical trials have established which patients might benefit from postmastectomy radiation therapy after upfront surgery, no such data exist for guiding decisions on who might benefit from postmastectomy radiation therapy after upfront chemotherapy. Insight must be drawn from non-randomised data to provide such guidance. Early data suggest that both extent of disease at presentation and response to neoadjuvant chemotherapy predict the risk of locoregional recurrence, and can be used to tailor recommendations for postmastectomy radiation therapy. Randomised clinical trial data are needed to assess whether postmastectomy radiation therapy can be safely omitted in selected women with good response to neoadjuvant chemotherapy.     

The role of radiation therapy in the management of the Hodgkin's disease

Radiation therapy has curative potential for patients with stage I-II disease, and five-year relapse-free survival rate in excess of 80% can be expected. Despite an advantage of chemotherapy combined with radiation therapy in improving relapse-free survival, no significant advantage has yet been demonstrated in allover survival. Patients with stage IIIA1 may also be treated radiation therapy alone with results of five-year survival rate of 53-60%. However, patients with stage IIIA2 should be treated with chemotherapy with or without radiation therapy combined.     

Contemporary management of prostate cancer with lethal potential

Screening for prostate cancer by determining serum prostate-specific antigen (PSA) levels has resulted in a stage migration such that patients with high-risk disease are more likely to be candidates for curative local therapy. By combining serum PSA, clinical stage, and biopsy information--both Gleason score and volume of tumor in the biopsy cores--specimen pathologic stage and patient biochemical disease-free survival can be estimated. This information can help patients and clinicians understand the severity of disease and the need for multimodal therapy, often in the context of a clinical trial. While the mainstays of treatment for local disease control are radical prostatectomy and radiation therapy, systemic therapy must be considered as well. A randomized trial has shown a survival benefit for radical prostatectomy in patients with positive lymph nodes who undergo immediate adjuvant androgen deprivation. Clinical trials are needed to clarify whether adjuvant radiation therapy after surgery confers a survival benefit. PSA is a sensitive marker for follow-up after local treatment and has proven that conventional external-beam irradiation alone is inadequate treatment for high-risk disease. Fortunately, the technology of radiation delivery has been dramatically improved with tools such as three-dimensional conformal radiation, intensity-modulated radiation therapy, and high-dose-rate brachytherapy. The further contributions of pelvic irradiation and neoadjuvant, concurrent, and adjuvant androgen deprivation therapy have been defined in clinical trials. Future management of high-risk prostate cancer may be expanded by clinical trials evaluating neoadjuvant and/or adjuvant chemotherapy in combination with androgen deprivation.     

Radiation therapy after radical prostatectomy: a review of the issues and options

The role of postoperative radiation therapy after radical prostatectomy is controversial. Radiation can be delivered as an adjuvant therapy in the immediate postoperative period for high-risk patients or as salvage therapy in the setting of a rising prostate-specific antigen. There are important issues that must be addressed when considering radiation therapy after prior prostatectomy. One issue is the determination of whether a patient has local disease amenable to salvage pelvic radiation or whether the patient has occult metastatic disease. In addition, the radiation oncologist must decide if an acceptable dose of radiation therapy can be administered safely to the prostate bed. There are no published randomized clinical trials on the topic of postprostatectomy radiation therapy, although several have completed accrual or are in progress. Based on the available literature, postoperative radiation is a safe option in the patient at high risk for local recurrence based on adverse pathology or clinical features (eg, extensive extracapsular disease, positive margins, high volume Gleason score >7, and so on). Administration of an adequate dose of prostate bed radiation (ie, >64 Gy) in men with these adverse prognostic features appears to effectively reduce prostate-specific antigen (PSA) recurrence rates. The protracted natural history of prostate cancer requires longer follow-up to determine if survival will be ultimately affected by adjuvant or salvage radiation therapy. Some urologists have advised a "wait and watch policy" for high-risk postprostatectomy patients. Administration of radiation therapy is done only if and when the PSA rises. However, data suggest this approach may have limited durability in high-risk prostate cancer and could reduce the likelihood of prolonged progression-free survival. This review summarizes published retrospective and prospective data to guide decision making in selecting appropriate candidates for postprostatectomy radiation therapy.     

The current status of combined radiotherapy and chemotherapy for locally advanced or resected pancreas cancer

Pancreas cancer is the fourth most common cause of cancer deaths. Even for the small percentage of patients who can undergo surgical resection of the primary tumor, the risk of recurrence remains unacceptably high. For patients with localized disease that is not amenable to surgical resection, pain related to the primary tumor can significantly impair quality of life. Attempts to improve the duration and quality of life for these patients have included both chemotherapy and radiotherapy. The addition of chemotherapy to radiation may enhance the local effects of radiation or provide treatment of disease outside the radiation field. The results of clinical trials evaluating the appropriate therapy for locally advanced or resected disease have been inconsistent. In some instances, the methods used in these studies became outdated before the results were available. Hopefully, advances in radiation techniques and systemic drug therapy will provide more durable and clinically relevant results. Meanwhile, treatment decisions should be tailored to the clinical situation, including consideration of treatment toxicity and therapy goals. Recognizing which patients are likely to benefit from combination therapy or systemic therapy alone is a subject of future and ongoing clinical trials.     

Radiation therapy for patients with locally advanced pancreatic cancer: Evolving techniques and treatment strategies

Despite ongoing efforts, patients with locally advanced pancreatic cancer (LAPC) continue to have a dismal prognosis. Such tumors are unresectable, and optimal treatment with chemotherapy and/or radiation therapy is still not established. While chemotherapy is conventionally aimed at preventing metastatic spread of disease, radiation therapy acts locally, improving local control which can potentially improve overall survival and most importantly quality of life. Here, we aim to review the primary literature assessing the role of diverse radiation therapy strategies for patients with LAPC.Many radiation regimens can be considered, and no standard treatment has demonstrated a clear improvement in clinical outcomes. We advise that the modality of choice be dependent on the availability of equipment, the dose and fractionation of treatment, as well as the dose received by normal tissue. Moreover, a candid discussion with the patient concerning treatment goals is equally as essential. Three notable strategies for LAPC are intensity-modulated radiation therapy, volumetric modulated arc therapy, and proton. These radiation modalities tend to have improved dose distribution to the target volumes, while minimizing the radiation dose to surrounding normal tissues. Stereotactic body radiation therapy can also be considered in LAPC patients in cases where the tumor does not invade the duodenum or other neighboring structures. Because of the high doses delivered by stereotactic body radiation therapy, proper respiratory and tumor motion management should be implemented to reduce collateral radiation dosing. Despite improved clinical outcomes with modern radiation modalities, evolving techniques, and more accurate planning, future studies remain essential to elucidate the optimal role for radiation therapy among patients with LAPC.     

Intracranial germ cell tumors

Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological information, but a subgroup of tumors will secrete specific tumor markers, including alpha-fetoprotein and beta-human chorionic gonadotropin, which may obviate the need for surgical intervention. The management of intracranial germ cell tumors in both children and adults remains unsettled. Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy. The dose and volume of radiation therapy needed for disease control is not well established, and controversy exists concerning the need for whole brain or craniospinal radiation therapy for localized tumors. Germinomas are also chemosensitive and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy. The outcome for patients with nongerminomatous germ cell tumors is less favorable. Radiation therapy alone will result in disease control in 40%-60% of patients. The addition of chemotherapy to radiation therapy may improve the rate of survival.     

Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy

Nineteen patients with Hodgkin's disease who relapsed primarily in nodal sites after intensive combination chemotherapy were retreated with wide-field radiation therapy alone or with additional chemotherapy between January 1971 and December 1984. Six patients presented in second relapse and 13 patients in first relapse. Seven patients were treated with combination chemotherapy and radiation therapy and twelve patients were treated with radiation therapy alone. Radiation therapy field sizes and doses were similar to those recommended for early-stage Hodgkin's disease patients treated with radiation therapy alone. The 5-year actuarial freedom from relapse (FFR) and survival following retreatment were 48% and 69%, respectively. Twelve patients are currently disease-free 12 to 172 months following retreatment. Wide-field radiation therapy alone or with additional chemotherapy should be considered for patients with advanced Hodgkin's disease who relapse in nodal sites after initial combination chemotherapy.     

Progressing prostate carcinoma

In the Karnell Cancer Center Grand Rounds, we present a patient who underwent radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive margins and subsequently developed local recurrence and then systemic disease. Pathologic and radiologic aspects of his disease are discussed. Therapeutic options at different stages of the disease are examined from the point of view of the urologist, radiation oncologist, and medical oncologist. The surgical portion of the discussion focuses on the selection of initial therapy. Both the selection of surgical candidates and choice of pre- or post-operative therapy in patients can be aided by prognostic tools looking at several variables, including prostate-specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle invasion, extracapsular invasion, and lymph node involvement. Low-risk patients can be treated with monotherapy, such as radical prostatectomy, external beam radiation therapy, prostate brachytherapy, or cryosurgical ablation of the prostate. Higher risk patients may require adjuvant and possibly neoadjuvant therapy in addition. The radiation portion of the discussion focuses on the use of radiation therapy as salvage for relapsing disease. Of particular importance is the point that treating high-risk patients whose PSA levels have started to rise but are less than 1 ng/ml results in a long-term PSA control rate as high as 75%, but that limiting the use of salvage radiation therapy to patients with high PSA levels or biopsy confirmation of local recurrence in the face of a negative bone scan results in biochemical long-term control of less than 40%. In the medical oncology part of the discussion, the major focus is on the use of chemotherapy to treat patients whose disease has become resistant to hormonal therapy. Mitoxantrone plus a corticosteroid has been found to offer significant palliation for such patients. Combination therapy with estramustine plus taxanes, other microtubule inhibitors, or other agents such as topoisomerase II inhibitors, has been found to cause shrinkage of measurable soft tissue disease and diminution of serum PSA levels. The development of effective hormonal and chemotherapeutic drugs for treatment of metastatic disease has led to new interest in adjuvant and neoadjuvant therapy of high-risk patients.     

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.     

Induction chemotherapy for non-small cell lung cancer with clinically evident mediastinal node metastases: the role of postoperative radiotherapy.

Survival for clinical Stage IIIa (T1-3, N2) non-small cell lung cancer is very poor because of poor local disease control and systemic spread. To address these shortcomings, we initiated a treatment program with induction chemotherapy, surgery, and postoperative radiation reserved for patients with residual disease at thoracotomy. Between 1984 and 1986, 41 patients with clinically evident N2 disease were treated with induction chemotherapy followed by resection and the selective use of intraoperative brachytherapy. All patients with tumor in the resection specimen received two cycles of chemotherapy and 15 patients received radiation therapy. With a median follow-up of 5.4 years, overall survival is 27% at 3 years, and 12% at 5 years. Despite the adverse selection process median survival is 19 months for patients receiving postoperative radiation therapy, and 22 months for the more favorable patients not requiring radiation therapy, supporting the selective use of postoperative radiation in this setting. In summary, this treatment has yielded good median survival and long-term survival for some of the patients. However, the ultimate value of this approach can only be determined by prospective trials which compare it to standard therapy.     

Durable efficacy of adjuvant radiation therapy for prostate cancer: will the benefit last?

Radical prostatectomy can be an effective therapy for men with organ-confined disease. However, extension beyond the confines of the prostate (pT3) can be found in many men, and this is often associated with longterm prostate-specific antigen (PSA) failure. Not all patients will progress with pT3 disease. The identification of additional adverse prognostic features (high Gleason score, PSA greater than 10 ng/mL, and seminal vesical invasion) can help identify those men at highest risk of progression following definitive surgery. The role of postoperative therapy in patients with high-risk features is often controversial. The lack of long-term survival benefit, toxicity, and cost are often cited. We reviewed our experience with a unified approach to this patient population and performed matched-pair analysis of patients with similar adverse prognostic features treated with and without postoperative radiation therapy. For our series, the results indicate that the addition of adjuvant radiation therapy is associated with a significantly reduced risk of PSA recurrence. The 5-year bNED rate after adjuvant radiation therapy was 89% (95% CI: 76% to 100%) compared with 55% (95% CI: 34% to 79%) after surgery alone (P = .002). This benefit also appears to hold true for men with pathological involvement of their seminal vesicles. A dose-response curve was observed with improved disease control above a level of 61.2 Gy. Appropriate patient selection and delivery of an adequate dose of radiation can improve the PSA recurrence of most patients with pT3 disease.     

Use of Sentinel Lymph Node Biopsy to Select Patients for Local–Regional Therapy After Neoadjuvant Chemotherapy

Use of sentinel lymph node biopsy for axillary staging of patients with breast cancer treated with neoadjuvant chemotherapy has been widely debated. Questions arise regarding the accuracy of sentinel lymph node biopsy in axillary staging for these patients and its use to determine further local–regional therapy, including surgery and radiation therapy. For patients who are clinically node-negative at presentation, sentinel lymph node biopsy enables accurate staging of the axilla after neoadjuvant chemotherapy, and determination of which patients should go on to further axillary surgery and regional nodal radiation therapy. Importantly, performing axillary staging after completion of chemotherapy, rather than before chemotherapy, enables assessment of response to chemotherapy and the extent of residual disease. This information can assist the planning of adjuvant treatment. Recent data indicate that sentinel node biopsy can also be used to assess disease response after neoadjuvant chemotherapy for patients with clinical N1 disease at presentation.     

Relapsed and Refractory Hodgkin's Lymphoma: New Avenues?

Relapse or progression following therapy for Hodgkin's lymphoma occurs in 10% to 60% of patients depending on initial clinical stage. Patterns of failure in advanced disease determine prognosis of salvage therapy. Progression or early relapse after less than 12 months requires intensive salvage therapy. Only late, isolated, asymptomatic relapse, which occurs in less than 25% of those relapsing from systemic therapy, can be treated with conventional-dose chemotherapy with or without radiation. Overall about 40% to 50% of relapses from advanced disease can be salvaged with higher percentages for patients relapsing from early stage disease.     

Orthovoltage intraoperative radiotherapy: a new look at an old idea

A 300 kvp orthovoltage machine has been permanently installed in an operating room for delivering intraoperative radiation therapy (IORT). A historical review of orthovoltage IORT and our present approach are described. The preliminary experience with 38 patients treated with orthovoltage IORT indicates that this technique is feasible, has low acute morbidity, and can be useful for palliation. "Radical" radiation therapy consisting of IORT "boost" treatment combined with external beam was used in 24 patients with primary or recurrent cancer. Local failure in 27 patients treated with IORT +/- external beam radiation therapy was 56%, but varied from 11% (1/9) for patients with resected disease to 78% (14/18) for patients with unresected disease. Complications occurred in nine patients (24%) and have been acceptable. There are 17 patients alive and six are NED, with follow-up of 4-18 months. There appears to be a role for orthovoltage IORT especially when combined with surgical resection for local control of advanced cancer arising in the abdomen where the use of high doses of external radiation therapy are hazardous.