The current role of interstitial thermo-radiotherapy.

Internal methods of thermotherapy such as interstitial, endocavitary and perfusional hyperthermia in combination with high- (HDR) or low-dose rate (LDR) brachytherapy have gained increasing interest among oncologists due to the known radio- and chemosensitizing potential of heat. Interstitial techniques offer several advantages over percutaneous heating techniques: confined treatment volume with improved sparing of normal tissue; accessibility of deeper tumors in various sites; more homogeneous distribution of therapeutic temperatures; and better control and evaluation of thermal parameters, when using extensive "thermal mapping" procedures. Currently several promising techniques are investigated such as radiofrequency (RF), microwave (MW) and hot source (HS) techniques. In phase 1 to 2 studies interstitial hyperthermia (IHT) has been mostly applied in the head and neck and brain, the chest wall, the pelvic region and the extremities for primary advanced, persistent or local recurrent tumors, which have responded poorly to conventional treatment approaches. Preliminary data on 600 patients treated with interstitial thermo-radiotherapy (IHT-IRT) are extremely promising despite broad variations among the technical and clinical treatment parameters. The tumor response rate in various clinical trials ranges between 11% and 74% CR, and with respect of extensive pre-treatment approaches, the overall complication rate of 20% appears acceptable. So far several prognostic treatment factors have been identified: tumor volume; radiation dose; high minimum tumor temperatures and sufficiently good thermal quality of the hyperthermia treatment. Future technical innovations should broaden clinical implementations of interventional hyperthermia such as intraoperative hyperthermia and intracavitary hyperthermia. It would appear from these experiences, that interstitial hyperthermia is an effective and safe treatment modality, especially when combined with radiotherapy for tumor palliation. Prospective randomized multicentric studies have already been initiated to investigate its role in palliative and adjuvant tumor therapy.     

Clinical trials with local (external and interstitial) irradiation and hyperthermia. Current and future perspectives

There is a growing body of experience in the clinical use of either external or interstitial (local) hyperthermia. A great deal has been learned about the technical and prognostic factors that influence the efficacy of heat combined with irradiation. Despite some technologic advances, substantial limitations remain to the optimal delivery of heat and monitoring of the temperature throughout the treatment volume with localized techniques. Additional efforts to improve present equipment are paramount, and further studies should be encouraged to establish the optimal conditions for the delivery and temperature monitoring of local hyperthermia combined with irradiation or cytotoxic agents. It is possible to induce tumor regression and produce satisfactory palliative results in selected groups of patients with recurrent or advanced tumors. The clinical application of hyperthermia, particularly in previously irradiated patients, should be continued. Adequately designed clinical trials to amplify our understanding of this modality and its optimal clinical applications should be strongly supported.     

Current state and possibilities of radiotherapy in the inter- disciplinary treatment of malignancies of the stomach, pancreas and bile ducts. I. Stomach cancer

Surgery is undoubtedly the therapy of choice in case of the advanced carcinoma of the stomach. In spite of more and more radical and extended operation techniques, the extremely unfavorable prognosis could not be improved. Based on experiences gained with palliative irradiations, the efficacy of radiotherapy can be considered to be proved. Its difficulties and problems are due to the topographic position of the stomach and to the radiosensitivity of the stomach and the adjacent organs. An additional application of radiotherapy seems sensible regarding the high rate of local recurrences and regional lymph node metastases following surgery (about 90%). The greatest effect of radiotherapy is to be expected in case of intraoperative application - alone or combined with postoperative percutaneous irradiation. However, the therapeutic effect of fast neutrons, hyperthermia, radiosensitizers has not been explored yet. The occurrence of remote metastases besides local recurrences in about 25% of all cases and the available results of some smaller studies suggest a therapeutic advantage to be obtained by an additional systemic cytologic therapy. The authors present the surgical, radiotherapeutic, and chemotherapeutic results achieved hitherto in the treatment of the advanced carcinoma of the stomach. Further possibilities for the future use of radiotherapy are proposed in order to encourage the establishment and application of interdisciplinary therapy conceptions.     

Local hyperthermia in the treatment of advanced tumors: curative and palliative effects

During the years of 1978 to 1981, a pilot study was conducted with 210 patients suffering from 235 tumors. The treatment included localized high-frequency hyperthermia alone or combined with radiotherapy and/or chemotherapy. The final evaluation of 164 tumors with different sites, sizes and histologic findings shows that even if the patients collective is unfavorably selected (nearly all tumors in an advanced stage), an increased palliative effect exceeding the clinical effect expected for radiotherapy alone was reached in 60 to 70% of all cases. 45% of the patients showed curative effects in the sense of an objectively improved tumor remission. At the same time, a significant reduction of local side effects of radiotherapy was achieved by the hyperthermic treatment. Localized hyperthermia until 42/43 degrees C has only a small rate of complications, even if it is applied in the abdominal region. Within the relatively short follow-up period, an increased rate of metastases after therapy combinations with hyperthermia was not observed.     

Tumorablation der Leber

Minimal-invasive techniques for ablation of primary and secondary hepatic tumors gain increasingly clinical importance. This is especially true since surgical resection and classic chemotherapy is successful only in a limited number of patients.Local ablative methods incorporate chemo- (percutaneous alcohol instillation, transarterial chemoembolization), thermo- (radiofrequency-, laser-, microwave-, cryoablation, high intensive focused ultrasound) and radio-ablative techniques (interstitial brachytherapy, selective internal radiotherapy). Regarding their implementation and specific effects these methods are varying widely, nevertheless all of them have a high therapeutical efficacy together with a low complication rate in common-correct application presumed. The knowledge on specific indications and contraindications is crucial to implement these methods into multimodality therapy concepts.     

Hyperthermia in tumor therapy

The application of hyperthermia in tumor therapy is expanded to a high degree. As affecting point in biological tissue the following is discussed: Cytotoxic effect with temperatures of 43 degrees C with alterations on cell membrane and in intermediate metabolism, injury of microcirculation, where--because of a pathological vascularisation--tumor tissue is affected in a stronger way than the better adapted vessel net of normal tissue. The radiosensitizing effect between 40 and 42 degrees C is of interest for radiologist. Degree and duration of temperature and the interval between irradiation and thermal application modify the amplifying thermal factor. As adjuvant therapeutic modality the hyperthermia can decrease the hypoxic radioresistant part of cells and is an additional palliative therapeutic measure. Indications within a curative radiotherapy are elaborated at present globally.     

Neoplasm treatment using hyperthermia and radiotherapy

The authors present the run of isotherms in muscle and fatty tissue/muscle phantoms after hyperthermia produced by a 13,56 MHz generator (different electrode sizes, influence of the cooling system) and the therapy results of 136 patients submitted to hyperthermia and irradiation. The local therapy results are remarkable in case of tumors of the ORL region, cervical lymph node metastases and superficial and semi-deep tumors. The subjective side effects are supportable, the objective side effects (complications of the combined therapy) are unimportant. The question whether the good results of palliative therapy justify a curative application cannot be answered yet. This has to be investigated by randomized prospective studies.     

Technical basis for the application of localized hyperthermia

Techniques of localized hyperthermia have been developed these last years. Very superficial tumors may be heated by infra-red radiation, radiative diathermy at high frequencies (2450 MHz) or even by techniques of contact hyperthermia. Superficial tumors (some cm deep) may be heated by radiative diathermy at lower frequencies (434 MHz or 915 MHz), inductive diathermy or ultrasound. Deeper tumors (about 10 cm deep) are the most problematic. They may be heated by capacitive diathermy at frequencies of 13.5 or 27 MHz under favourable conditions, or perhaps by ultrasound when multiple transducers are used. Hyperthermic extracorporeal perfusion (in limbs) and interstitial hyperthermia are efficient and promising techniques but their indications are limited.     

经皮穿刺植入125I粒子治疗恶性肿瘤的临床应用

目的根据内放射源125I粒子的物理特性探讨其治疗原理、治疗计划系统(TPS)的意义、治疗方式及临床疗效.方法18例晚期肿瘤患者采取经皮穿刺植入125I粒子行组织间放疗.结果18例肿瘤患者均未出现任何严重的并发症,生存质量明显提高.2个月后经胸片、CT复查18例患者肿瘤均有不同程度缩小,12例明显缩小,其中5例肿瘤基本消失.结论短期疗效证明,125I粒子组织间放疗对晚期肿瘤效果显著,不良反应小.     

Präoperative Bestrahlung mit interstitiellem Radiohyperthermie-Boost bei Mammatumoren ≥3 cm

Aim

The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia.

Patients and Methods

One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy¹⁹²Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 × 2 Gy/week. Local hyperthermia with 43.5–44.5°C over 60 minutes was delivered immediately before interstitial radiotherapy.

Results

One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases.

Conclusion

In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.     

Local hyperthermia combined with radiotherapy, chemotherapy, or arterial chemoembolization

Local hyperthermia combined with radiotherapy, chemotherapy, or arterial chemoembolization was performed in 31 patients with malignant tumors using an HTM 3000 heater. The response rate was 41.9%. Fifteen patients with superficial tumors had a high rate of response (60%). Response was particularly good (75%) when radiotherapy was also used. In contrast, the response rate was low (25%) in 16 patients with deep seated tumors. However, the criteria for assessment might not be appropriate. If improvement in symptoms and intratumorous changes were also considered, the therapy was judged to be valuable in 56.3% of the patients. No adverse reactions of concern developed except in some special cases. Hyperthermia with the HTM 3000 heater was safe.     

Trials of combined radiation and hyperthermia with various heating modalities in cancer therapy

A microwave heating apparatus with a frequency of 2,450 MHz and an inductive radio-frequency heating apparatus were developed for hyperthermia for cancer therapy, and clinical trials of combined radiation and hyperthermia were conducted. During the same period, a capacitive type radiofrequency unit was used. The tumors included superficial tumors, cancer of the uterine cervix, recurrent tumors at the stump of the cervix, and some deep-seated tumors. Cases showing complete response were as follows: 5 out of 13 cases treated with 2,450 MHz heating for superficial tumors, 8 out of 17 cases treated with 2,450 MHz intracavitary heating, and 2 out of 15 cases treated with radiofrequency heating. A feasibility study of various heating modalities was performed.     

Hyperthermia in cancer treatment

Hyperthermia, used as an adjunct to radiation therapy, can increase tumor regression significantly. When used as a local (as opposed to regional or systemic) modality, proper treatment requires detailed knowledge of tumor and normal tissue geometry, and physiologic parameters such as perfusion and thermal conductivity. A brief review of local heating techniques and details of two techniques used to treat brain tumors are provided: Scan Focused Ultrasound and Interstitial Ferromagnetic Seed Implants. These techniques require the most sophisticated use of diagnostic radiology methods. Data from several modalities such as CT, MRI, angiography, and xenon CT perfusion studies must be merged into a consistent data set. This data set must be indexed precisely relative to the treatment apparatus. Real-time noninvasive temperature monitoring of the treatment field has not been achieved at this time, but is of interest to researchers in hyperthermia.     

Radiofrequency ablation of pulmonary tumors

The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease.     

Interstitial hyperthermia of the prostate in combination with brachytherapy

Objective

A retrospective study to evaluate the feasibility and toxicity of interstitial hyperthermia (IHT) combined with high-dose-rate (HDR) brachytherapy as the initial treatment for low- and intermediate-risk prostate cancer, and as a salvage therapy in previously irradiated patients with local recurrence.

Patients and methods

Between 18 December 2008 and 5 September 2012, 73  prostate cancer patients were treated with interstitial HDR brachytherapy of the prostate combined with IHT. In 54 patients this was the initial therapy for prostate cancer, while the other 19 were treated for local recurrence after previously undergoing external beam radiotherapy (EBRT). Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 within 3 months after treatment.

Results

Median follow-up was 15 months (range 3–46). The combination of HDR brachytherapy and IHT was well tolerated. The toxicity profile was similar to that of HDR brachytherapy when not combined with hyperthermia. The most common minor complications were urinary frequency (grade 1: 37?%; grade 2: 22?%), nocturia (three times per night: 29?%; four- or more times per night: 20?%) and transient weakening of the urine stream (grade 1: 36?%; grade 2: 11?%). No early rectal complications were observed in the patient group and the severity of genitourinary toxicity was only grade 1–2.

Conclusion

Early tolerance of IHT in combination with HDR brachytherapy is good. Further prospective clinical studies should focus on the effects of combining IHT with HDR brachytherapy and the influence of this adjuvant therapy on biochemical disease-free survival, local control and overall survival.     

Computed tomography guided interstitial percutaneous high-dose-rate brachytherapy in the management of lung malignancies. A review of the literature

A growing number of patients with lung cancer are not amenable to surgery due to their age or comorbidities. For this reason, local ablative techniques have gained increasing interest recently in the management of inoperable lung tumors. High-dose-rate percutaneous interstitial brachytherapy, performed under CT-guidance, is a newer form of brachytherapy and is a highly conformal radiotherapy technique. The aim of this study was to describe this method and review the existing literature. Eight articles comprising 234 patients reported toxicity and clinical outcome. The follow-up ranged from 6 to 28 months. Diverse fractionation schemes were reported, with 20 Gy in a single fraction being the most frequently utilized. Toxicity was limited; major pneumothoraces occurred after only 8% of the interventions. Local control rates at one year ranged between 37% and 91%. In conclusion, high-dose-rate percutaneous interstitial brachytherapy is a safe, fast, and efficient treatment option for inoperable lung tumors.     

Nuclear magnetic resonance in oncologic radiotherapy

The possibilities of utilizing Nuclear Magnetic Resonance in Radiation Oncology are examined, on the basis of information provided by spectroscopy (MRS), studies on the tissues characterization of tumors, and preliminary practical application of imaging (MRI) to radiation therapy. MRS affords information on the bioenergetics of the tumor cells, and on the biochemical changes induced by ionizing radiation; further, some results of clinical importance were obtained in "monitoring" tumor response to radiation therapy and chemotherapy. Tissue characterization of normal tissues and of tumor is analyzed; technical factors, morphological elements, and structural elements are considered. Morphological elements include anatomical recognition, clinical and radiological evaluation, appraisal of the peritumoral tissues, and analysis of inhomogeneities. Among structural elements are considered some methods suitable to achieve a full evaluation of tissue characterization of tumors, on the basis of an appropriate employment of sequence parameters. Practical application of MRI on radiotherapy of tumors comprises staging procedures, contribution to the selection of differentiated radiation volumes for radiotherapy planning, and new data on the evaluation of biological effects of ionizing radiation on normal tissues of patients.     

Imaging hypoxia in tumors

For many years, it has been known that hypoxia affects the response to radiotherapy in human cancers. Hypoxic regions can develop as a tumor grows beyond the ability of its blood supply to deliver oxygen to the full extent of the tumor, exacerbated by vascular spasm or compression caused by increased interstitial fluid pressure. However, hypoxia is heterogeneous, and tumors that appear identical by clinical and radiographic criteria can vary greatly in their extent of hypoxia. Several invasive procedures to measure hypoxia in tumors have been developed and are predictive of response to therapy, but none of these is in routine clinical use because of technical complexity, inconvenience, and inability to obtain repeated measures. Noninvasive imaging with a hypoxia-directed radiopharmaceutical could be of great clinical utility. Most such radiopharmaceuticals under development use 2-nitroimidazole as the targeting moiety. 2-Nitroimidazole, which is selectively reduced and bound in hypoxic tissues, has been labeled with F-18, Cu-64/67, I-123, and Tc-99m. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA) have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91), have also been evaluated. In particular, 1-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors.     

质子束放疗在肿瘤中的研究进展

肿瘤放疗的基本准则是提高肿瘤靶区的放射剂量,同时更好地保护肿瘤周围的正常组织器官。质子束治疗（PBT）是目前全球最先进的放疗技术之一,其能更好地体现这一准则。理论上,质子束以其特有的Bragg峰和优越的相对生物学效应,可给予肿瘤靶区最大剂量,同时降低肿瘤周围正常组织器官的接受剂量,实现对肿瘤靶区的“定向爆破”,提高肿瘤的局部治疗率和控制率,优于传统光子治疗。目前已应用于临床的研究包括黑色素瘤、肺癌、食管癌、乳腺癌、肝癌、前列腺癌和儿童恶性肿瘤等多种病变,但多为回顾性研究,而且建立和维护质子设备的成本巨大,因此用PBT治疗恶性肿瘤尚存争议。PBT面临的挑战是缺乏足够的临床证据和不明确的生物学效应等,克服这些不足可能会更好地促进PBT的快速发展。笔者详细论述了PBT的物理、生物学特性及其在肿瘤治疗中的研究和应用进展。     

Role of radiology in the treatment of malignant hilar biliary strictures 1: review of the literature

Malignant strictures of the biliary tree are an uncommon cause of obstructive jaundice. There are a number of pathological subtypes, but tumours in this region tend to have similar clinical and diagnostic features and therapeutic and prognostic implications. We review the published literature on this topic discussing diagnostic modalities and treatment options with a focus on radiological intervention. Diagnosis currently is best achieved using a range of procedures. Direct cholangiography remains the gold standard in delineating anatomy, but the invasiveness of this procedure limits its use as a purely diagnostic tool. Magnetic resonance technology, in particular magnetic resonance cholangiopancreatography, has an increasing role as accessibility is improved. Treatment of these tumours is difficult. Surgical resection and palliative biliary enteric bypass are the most common methods used with endoscopic and percutaneous therapies reserved for palliating patients not fit for surgery. There is little firm evidence to suggest that any one palliative modality is superior. Interventional radiology is particularly suitable for palliative management of difficult and expansive lesions as the anatomy can preclude easy access by surgical or endoscopic techniques. Good palliative results with minimal mortality and morbidity can be achieved with percutaneous stenting.