Cryotherapy, electrocautery, and brachytherapy

Since it was first used 70 years ago, brachytherapy has become an effective tool in the treatment with tracheal bronchial malignancy including primary and recurrent bronchogenic carcinoma and metastatic carcinoma. The technique has evolved from interstitial implantation of radioactive sources directly to the tumor using rigid bronchoscopy to intraluminal placement of a radioactive source into a polyethylene afterloading catheter placed using FB. Intraluminal brachytherapy is effective in palliating complications caused by malignant endobronchial tumors such as dyspnea, hemoptysis, intractable cough, atelectasis, and postobstructive pneumonia. Brachytherapy may be combined with external beam radiation, Nd:YAG laser therapy, and chemotherapy to enhance the palliative treatments of patients. The risk of severe complications from brachytherapy may be caused more by location of tumor being treated rather than those fractionations scheme. When tumor involves the mainstem bronchi and upper lobes, it seems prudent to obtain CT to exclude tumor invasion of the pulmonary arteries or considerable destruction of the bronchial wall and mediastinal invasion of the tumor. Patients with findings such as these should not be treated with endobronchial brachytherapy or treated with LDR brachytherapy. Brachytherapy is proved to be effective and a safe palliative treatment for endobronchial malignancies, but further investigations are necessary to determine the optimal dose scheme and its efficiency in bronchogenic carcinoma and combined with external beam radiation therapy or surgery or other endobronchial procedures such as Nd:YAG laser or cryotherapy.     

Intraluminal brachytherapy and selfexpandable stents in nonresectable biliary malignancies--the question of long-term palliation.

BACKGROUND/AIMS: To evaluate the effect of a combination of intraluminal brachytherapy and metallic stent implantation in the treatment of patients with nonresectable biliary tumors. METHODOLOGY: Thirty-two patients aged 41-80 years with nonresectable biliary malignancies--Klatskin's tumor (n = 17), gallbladder carcinoma (n = 11) and carcinoma of papilla Vateri (n = 4)--were treated with a combination of intraluminal brachytherapy (source Ir192, high-dose radiation regimen, total dose 30 Gy) and metallic stent implantation. Intraluminal brachytherapy and stent insertion (metallic, spiral-Z stent) were performed percutaneously in all patients. RESULTS: The mean survival in patients with Klatskin's tumor was 457 days (range: 64-1186; median: 358 days), in patients with gallbladder carcinoma 237 days (range: 92-609; median: 210 days) and in patients with carcinoma of papilla Vateri 850 days (range: 48-1518; median: 1277 days). The rate of 2-year survival in these groups as 27, 0 and 50%, respectively. The survival time differed significantly at the 5% level. The mean time of stent patency was 418, 220 and 850 days, respectively. No complications related directly to intraluminal brachytherapy were observed. CONCLUSIONS: Intraluminal brachytherapy combined with stent implantation is a safe method and appears to prolong survival in inoperable patients with Klatskin's tumor and carcinoma of papilla Vateri compared with nontreated patients in previous studies. In contrast no similar effect should be expected in patients with gallbladder carcinoma.     

Successful treatment of a T1 cancer of the pancreatic head with high dose rate brachytherapy and external radiotherapy

In this report, a unique case of a localized (T1N0M0) adenocarcinoma of the head of the pancreas is presented, which was successfully treated with interstitial high dose rate brachytherapy combined with percutan irradiation after biopsy. A total dose of 18 Gy was delivered with brachytherapy (6 Gy per fraction on three consecutive days) to the tumor via after-loading catheter. Brachytherapy was followed by external radiotherapy, delivering an additional dose of 46 Gy (18 MV-x) with four-field technique using conventional fractionation (2 Gy/day). Thirty-six months after completion of the treatment the patient is alive with no evidence of disease. The combination of interstitial high dose rate brachytherapy and external beam radiation therapy may be an effective tool to deliver curative dose without any significant sequelae in the treatment of operable pancreatic carcinoma, when the patient's condition contraindicates surgery.     

Endobronchial radiation therapy for obstructing malignancies: Ten years' experience with iridium-192 high-dose radiation brachytherapy afterloading technique in 365 patients

From 1983 to 1993, 365 patients with obstructing endobronchial malignancies were treated by endobronchial high-dose radiation (HDR) iridium-192 afterloading. In 346 patients, the objective was palliation, and in 19, the objective was curative. A dose of 5 Gy at 10 mm from the source axis was administered on three (palliation) and four (cure) occasions, at intervals of 14 days. The majority of patients were treated after exhaustion of external beam radiation therapy (EBRT), often in conjunction with other interventional bronchologic modalities such as endobronchial laser resection. Of the patients, 65% had a squamous cell carcinoma. Endobronchial HDR brachytherapy results in few acute complications and can be performed with no major discomfort on an outpatient basis. In approximately 66% of patients, a palliative effect is achieved, even after the exhaustion of conventional treatment. Life may be prolonged for a few months, but the enhancement of survival is difficult to assess for several reasons. Mean survival is 9 months for limited disease and 5 months for extensive disease. Endobronchial HDR brachytherapy influences the pattern of failure: a 21% rate of fatal hemorrhages is probably the result of the selection of patients for this treatment rather than a treatment-related complication. There is sufficient evidence to suggest the rational use of HDR brachytherapy in combination with EBRT to effect a cure, or even on its own when tumor growth is strictly limited. However, the standardization of radiotherapy and endoscopic indications is an urgent priority. Prospective, controlled, and cooperative studies are mandatory. Endobronchial iridium-192 HDR brachytherapy complements endobronchial laser resection and is currently an established technique in the treatment of advanced malignant airway obstructions.Offprint requests to: Priv. Doz. Dr H.-N. Macha     

Clinical outcomes and prognostic factors for patients with early esophageal squamous cell carcinoma treated with definitive radiation therapy alone

GOALS AND BACKGROUND: There are great differences between treatment methods for early-stage esophageal cancer in institutions. Radiation therapy has been considered to be an effective modality as organ-preserving treatment of the disease. The aim of this study is to assess the effect and limitation of radiation therapy on patients with early esophageal cancer. STUDY: The subjects were 38 patients with stage I (T1N0M0) squamous cell carcinoma of the esophagus who had received definitive radiation therapy alone. Eleven tumors were assessed within the mucosal layer, whereas 27 tumors showed submucosal invasion by examination using endoscopic ultrasound. All patients were treated with more than 60 Gy using a conventional daily fractionation dose at 2 Gy. An additional boost with brachytherapy was performed for 20 patients, and the prescribed doses were 10 Gy (5 Gy x 2 times) with low dose rate (8 patients) and 9 Gy (3 Gy x 3 times) with high dose rate (12 patients). Outcomes and prognostic factors, including the efficacy of intraluminal brachytherapy, were investigated. RESULTS: The cause-specific survival rate and the local control rate at 5 years were 82.6% and 86.3%, respectively. Recurrences were noted in 8 patients with submucosal cancer, but no recurrence was observed in patients with mucosal cancer. In the present study, tumor length was a statistically significant prognostic factor for cause-specific survival (P = 0.018) and tumor depth tended toward statistical significance (P = 0.073). In 27 patients with submucosal cancer, the tumor length was also statistically significant for the survival (P = 0.032). The 5-year cause-specific survival rates for the short tumor group and the long tumor group were 85.7% and 55.6%, respectively. On the other hand, the use of intraluminal brachytherapy had no significant effect on patient survival. CONCLUSION: Radiation therapy is very effective for early esophageal squamous cell carcinoma with tumor length less than 5 cm, but other treatment modalities, including chemoradiotherapy especially for inoperable patients, should be considered for submucosal cancer with a tumor length of 5 cm or more.     

Palliative therapy in cholangio- and gallbladder carcinoma

Non-resectable cholangiocarcinoma and gallbladder carcinoma have a poor prognosis. In addition to the general aspects of "best supportive care", biliary drainage is an important part of the palliative treatment of patients with malignant biliary stenosis. Photodynamic therapy has led to an improved median survival in hilar cholangiocarcinoma in two controlled studies. The survival benefit of external radiation or intraluminal brachytherapy has not yet been convincingly demonstrated. Whether or not systemic chemotherapy should be applied is still under debate. A single study including advanced biliary and pancreatic cancer patients has demonstrated a survival benefit for the combined group. In recent years, new chemotherapy protocols have been applied, some with promising results. Intra-arterial chemotherapy and chemotherapeutically coated stents have not been evaluated well enough to be recommended outside clinical studies. Ablative therapies have been used in a limited number of patients only. Further studies are necessary to clarify whether these treatment modalities are effective.     

Transduodenal intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region

BACKGROUND/AIMS: The prognosis of carcinomas of the subhepatic region is poor, and therapeutic efforts are limited mostly to palliation. The aim of this study was to retrospectively evaluate the effectiveness of transduodenal administration of intraluminal high dose rate brachytherapy in the palliative treatment of bile duct and pancreatic head carcinomas. METHODOLOGY: Twelve patients with inoperable bile duct and pancreatic head carcinomas were treated by transduodenal brachytherapy using high dose rate remote afterloading system. Eleven patients were treated by intraluminal brachytherapy inserted via a nasobiliary drain and one patient by intraluminal brachytherapy via a nasopancreatic drain inserted in the duct of Wirsung. RESULTS: After transduodenal intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated with the mean survival of 284 days. CONCLUSIONS: Transduodenal intraluminal brachytherapy is technically feasible. The addition of intraluminal brachytherapy may be beneficial to patients in whom drainage can be established. Transduodenal insertion of brachytherapy is not competitive to the percutaneous approach but spreads the possibilities of the treatment of bile duct carcinoma. Intraluminal brachytherapy of pancreatic head carcinoma is feasible only via transduodenal approach.     

Intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas

BACKGROUND/AIMS: The prognosis of biliary tract carcinomas is poor, and therapeutic efforts are limited mostly only to palliation. The aim of this study was to retrospectively evaluate the effectiveness and tolerability of intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas. METHODOLOGY: Thirteen patients with bile duct and gallbladder carcinomas were treated by brachytherapy administered through high dose rate remote afterloading system. Five patients after Roux-en-Y hepaticojejunoanastomosis were treated by intraluminal brachytherapy inserted via a diahepatal drain, and 8 inoperable patients were treated by intraluminal brachytherapy via a percutaneous biliary drain. RESULTS: After intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated and mean survival was 275 days. CONCLUSIONS: The addition of intraluminal brachytherapy may be beneficial to patients with carcinomas causing biliary obstruction in whom bile drainage can be established.     

Multimodality therapy using brachytherapy for caval tumor of hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) invading the inferior vena cava will expose patients to a risk of sudden death. Effective therapeutic approaches have not been established for caval tumor. This pilot study was conducted to evaluate the feasibility, safety, and clinical efficacy of multimodality therapy using endovascular brachytherapy with iridium-192 for caval tumor. METHODOLOGY: Six consecutive patients underwent endovascular high-dose-rate brachytherapy. An iridium-192 source was placed adjacent to the caval tumor through a vascular sheath introduced via the femoral vein. The total dose of brachytherapy ranged from 10 to 14Gy (5-7Gy per fraction). Hepatic arterial infusion chemotherapy was used in combination in all patients and external-beam radiotherapy was performed in 5 patients. RESULTS: Endovascular brachytherapy was technically successful in all patients. There were no complications related to brachytherapy. The median period of follow-up was 14.5 months (range, 3-29 months). Complete response and partial response were achieved in 2 (33%) and 4 (67%) patients, respectively. The 1- and 2-year survival rates were 50% and 17%, respectively, with a median survival of 14 months. CONCLUSIONS: Multimodality therapy using endovascular brachytherapy was a feasible, safe, and effective treatment for patients with advanced HCC invading the inferior vena cava.     

Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer： Results of feasibility study

AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer. METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial. Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54, 57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course. RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Karnofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35%. No patient suffered more than grade III acute toxicities induced by radiotherapy. CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.     

Approach to the patient with anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma is the least common but most lethal of thyroid cancers. All patients are classified as stage IV, with the primary lesion restricted to the thyroid gland in stage IVA; locoregional lymph nodes may exist in IVA/IVB; and IVC disease is defined by distant metastases. Prognosis is highly dependent on disease extent at presentation, and staging and establishing a plan of care must be accomplished quickly. Although almost all studies are biased due to their retrospective nature, the most important factors associated with longer survival are completeness of surgical resection (achievable in only a minority of patients) and high-dose (>40 Gy) external beam radiotherapy (preferably intensity modulated radiation therapy). Recent reports suggest that a multimodal approach (surgery, radiation, and chemotherapy) is beneficial. Given the high lethality even with apparent local disease, combination systemic therapy (cytotoxics and/or targeted agents) may improve outcomes in stage IVA/IVB patients. Newer, more effective drug combinations are urgently needed for IVC patients who want aggressive therapy. A candid discussion of the prognosis and management options, including palliative care/hospice, should be held with the patient and caregiver as soon as possible after diagnosis to clarify the patient's preference and expectations. Prospective multicenter clinical trials, incorporating molecular analyses of tumors, are required if we are to improve survival in anaplastic thyroid carcinoma.     

Ösophagus- und Magenkarzinom

There are several different approaches available for the palliation of esophago-gastric cancer. The decision on which type of therapy is used should be made individually based on an interdisciplinary consensus.In case of inoperable esophageal carcinoma, it becomes the primary objective of the therapy to maintain oral nutrition. This can be achieved through the insertion of self expanding metal stents as a minimally invasive procedure which results in an immediate elimination of dysphagia. As alternative and/or complementary therapy, radiological techniques (external beam radiation, brachytherapy) can be applied. Other locally endoscopic techniques (laser, APC-beamer) are often used for treating local complications of esophageal and inoperable stomach carcinomas. For these carcinomas palliative chemotherapy with cisplatin has been established as a standard regimen.     

Conformal radiation therapy for liver metastasis of esophageal carcinoma

Recently, aggressive hepatectomies or hepatic arterial infusion chemotherapy for liver metastasis from gastric or colorectal carcinoma have been performed, and the number of successful studies of liver metastasis have increased. However, there have been few successful cases of liver metastasis from esophageal carcinoma by surgery or chemotherapy. Herein, we show the benefits of radiation therapy for the treatment of liver metastasis from esophageal carcinoma. A 60-year-old woman with a 5-cm solitary liver metastasis from esophageal squamous cell carcinoma was treated with radiation therapy. The treated volume was encompassed by the anteroposterior and right lateral opposing fields, shaped by a multileaf collimator. The daily fraction size was 1.8 Gy, 5 days per week, for a total dose of 54 Gy. During the course of treatment, the patient did not experience any complications. After radiotherapy, abdominal computed tomography showed that the enhanced solid tumor had changed to a very low-density mass lesion with a clear margin, and the size was decreasing gradually between the 6 months. Radiotherapy could be a treatment of choice in patients with liver metastasis from esophageal squamous cell carcinoma.     

High-dose-rate endobronchial brachytherapy in endobronchial metastatic malignant chondroid syringoma.

A 65-year-old man with malignant chondroid syringoma (MCS) was found to have pulmonary metastases in the form of multiple pulmonary nodules 4 years after wide excision and adjuvant radiotherapy of a primary abdominal wall tumor. Atelectasis of the lingula due to obstructive endobronchial metastasis, resistant to combination chemotherapy, led us to perform high-dose rate (HDR) endobronchial brachytherapy for the first time in this rare tumor with a favorable response. This case emphasizes the role of HDR brachytherapy as a palliative procedure in endobronchial tumors not responding to other treatment modalities, even those considered to be radioresistant.     

An unusual case of Merkel cell carcinoma

Purpose Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin mainly found in elderly white patients. Due to its poor prognosis with distant metastases in up to 33% and local recurrence in 25–33% and a 5 year disease-specific survival of 64% (1–2) its early diagnosis and appropriate treatment is mandatory. Methods The study is an exceptional clinical case of a patient with a large inoperable MCC unable to be treated according to treatment guidelines due to her old age. We review the literature addressing treatment options. Results The patient was treated with palliative definitive radiotherapy to her large MCC of the left lower leg. She showed a rapid clinical response to four palliative radiation doses of 7 Gy each, necrosis of tumor mass and persistent clearing at a follow-up of 32 weeks. Our patient was very unusual in terms of her extensive MCC and her rapid and complete response to palliative radiotherapy lasting for 6 months at present. Conclusions As MCC is an aggressive tumor, best survival is achieved with early diagnosis in a localized stage and prompt adequate surgery and further stage-adjusted treatment. Thus, the differential diagnosis of MCC should not be dismissed in a reddish nodule on the leg, and every excision should be submitted to pathology. In accordance with the literature we demonstrate here that definitive radiotherapy is an effective treatment option for inoperable MCC, which in this individual patient produced necrosis of the extensive tumor mass after only four palliative doses.     

A case of gallbladder carcinoma with infiltration into the muscular layer that resulted in relapse and death from metastasis to the liver and lymph nodes

An eighty-six-year old woman was submitted to simple cholecystectomy and choledocholithotomy for acute obstructive cholangitis due to cholecysto-choledocholithiasis. At the operation, neither lymphogenic nor hematogenic metastasis was observed. Grossly, a protuberant lesion with an uneven surface and obscure borders was seen spread over the fundus and the body of the resected gallbladder. Histologically, it was a well-differentiated adenocarcinoma with slight invasion to the muscular layer. The patient died of recurrent carcinoma three years and eight months after the operation. At autopsy, multiple metastatic tumors were found in both lobes of the liver, and many lymph node metastases around the hilus of the liver, hepatoduodenal ligament and pancreas were also observed. It is strongly believed that gallbladder carcinomas that infiltrate the muscular layer should be classified as early-stage carcinomas with a fair prognosis, together with mucosal carcinomas. However, on the basis of the present case of relapse following simple cholecystectomy as described above, radical cholecystectomy including a wedge resection of the liver and dissection of the regional lymph nodes would seem necessary even for gallbladder carcinoma with infiltration into the muscular layer.     

Intraluminal high dose rate brachytherapy of tumorous esophageal stenoses

BACKGROUND/AIMS: The prognosis of inoperable carcinomas of esophagus is poor, and therapeutic efforts are generally limited to palliation. The aim of this study was to retrospectively evaluate the effectiveness of intraluminal high dose rate brachytherapy in the palliative treatment of tumorous esophageal stenoses. METHODOLOGY: Between February 1997 and July 2002 intraluminal brachytherapy was performed in 19 patients with inoperable esophageal carcinoma (squamous cell carcinoma in 14 cases and adenocarcinoma in 5 cases). All patients had dysphagia at presentation. Brachytherapy was performed using high dose rate afterloading system. RESULTS: Dysphagia was improved in all patients. The mean survival was 248 days. No mechanical complications were observed during introduction of the applicator. CONCLUSIONS: Our experience indicates that intraluminal brachytherapy is an effective and safe method of palliation of dysphagia caused by malignant esophageal stenosis.     

Neuroendocrine carcinoma of the parotid gland

INTRODUCTION: Neuroendocrine carcinomas are rarely observed in the parotid gland. CASE REPORT: A 65-year-old woman with an uneventful history was hospitalised for a tumor in the left parotid gland which had progressed for 8 months. The clinical manifestations and the radiological findings were in favour of a malignant process involving the parotid gland. Search for local and regional extension was considered to be negative. The surgical procedure was very difficult but enabled conservative resection of the tumor by total parotidectomy. Pathology results were in favour of a neuroendocrine carcinoma of the parotid gland. External radiotherapy was proposed, but interrupted by the patient after having received 40 Gy. After a 13 month follow-up, the patient was in good general condition without any sign of relapse or metastasis. CONCLUSION: Parotid neuroendocrine carcinomas are rare but need to be individualized owing to their poor prognosis with frequent occurrence of hepatic and pulmonary metastasis.     

Six cases of thymic carcinoma: a clinical review]

Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.     

Non-surgical treatments of esophageal cancers

INTRODUCTION: Despite improvements in surgical techniques and perioperative mortality, only slight improvements in the 5-year survival of patients with esophageal cancer have been observed in the last 20 years. Many patients with apparently localized cancer will have recurrences or metastatic disease despite surgery with curative resection. Consequently, multimodal therapies, including chemotherapy and radiotherapy, were introduced. This review outlines and critically analyzes current non-surgical treatments, including palliative care. CURRENT KNOWLEDGE AND KEY POINTS: Esophageal cancers appear to be chemosensitive but the median duration of response is short and toxicity consistent, especially in metastatic disease. Consequently, palliative chemotherapy should be offered preferably within a clinical trial. Chemotherapy as the only adjuvant treatment cannot be recommended outside clinical trials. Radiotherapy alone as a curative treatment has been proven to be inferior to chemoradiotherapy in inoperable tumors. Some data support the use of preoperative chemoradiotherapy, but randomized trials are conflicting. A pathological complete response has been identified as a favorable prognostic factor for survival. Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant dysphagia and can be considered as the reference treatment in patients with obstruction of the lower esophagus or with fistula. FUTURE PROSPECTS AND PROJECTS: Taxanes should be evaluated in randomized studies using chemotherapy or chemo-radiotherapy. Progress in radiotherapy, such as accelerated fractionation, greater radiation dose, and the addition of brachytherapy, will increase locoregional control and probably survival. The role of secondary surgery in patients responding to chemoradiotherapy still needs to be answered.