Janusz Skowronek

Hyperthermia - description of a method and a review of clinical applications

Summary The aim of this paper is to give a concise description of hyperthermia and a brief review of its clinical applications. Hyperthermia (HT, thermal therapy) is thought to be one of the cancer therapies and is considered to be an artifi cial way of increasing the body tissue temperature by delivering heat obtained from external sources to destroy cancerous cells or prevent their further growth. The fi rst principles of hyperthermic biology are presented. The phenomena of thermotolerance and radiosensitization are briefl y described, as well as the concept of thermal dose delivered to the tissues. Three main clinical applications of HT are presented. They include local, regional or part-body HT and whole-body HT that deliver heat to localized, advanced or deep-seated and disseminated malignancies, respectively, depending on location, depth and staging of the tumour. Energies used to apply heat to the tumour include microwaves, radiofrequency energy, ultrasound, infrared radiators and different kinds of hot sources (hot water, ferromagnetic seeds, nanoparticles, resistive implants). General indications for each HT subtype and possible combinations of HT with other cancer treatment modalities are presented. Substantially, HT is used as an adjuvant therapy and in such a role it is being evaluated in many clinical randomized trials throughout the scientifi c medical centres. Their fi rst preliminary results are already available, but still time is needed to produce fi rm conclusions and strict indications for hyperthermia treatment.

Esophageal stenting for benign and malignant disease : European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong recommendation, low quality evidence). 2 ESGE suggests consideration of temporary placement of SEMSs as therapy for refractory benign esophageal strictures (weak recommendation, moderate evidence). Stents should usually be removed at a maximum of 3 months (strong recommendation, weak quality evidence). 3 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures, because of their lack of embedment and ease of removability (weak recommendation, low quality evidence). 4 For the removal of partially covered esophageal SEMSs that are embedded, ESGE recommends the stent-in-stent technique (strong recommendation, low quality evidence). 5 ESGE recommends that temporary stent placement can be considered for treating esophageal leaks, fistulas, and perforations. The optimal stenting duration remains unclear and should be individualized. (Strong recommendation, low quality evidence.) 6 ESGE recommends placement of a SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive esophageal variceal bleeding (strong recommendation, moderate quality evidence).

Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer - between options.

Purpose Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy. Conclusions Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates.

High-dose-rate and pulsed-dose-rate brachytherapy in palliative treatment of head and neck cancers

PURPOSE The main purpose of the study was to assess the results of high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) in the palliative treatment of patients with locally or regionally recurrent head and neck cancers. The detailed aims concerned the evaluation of these methods in the context of local control, survival, and complications rates in patients subgrouped by different parameters such as age, gender, primary and recurrent tumor localization, tumor size, treatment method (HDR/PDR), primary treatment method, and radiation dose applied. METHODS AND MATERIALS PDRBT and HDRBT were used in 106 and 50 patients, respectively. In 8 patients, BT procedures were performed in combination with simultaneous chemotherapy. Sixteen patients were additionally treated with interstitial hyperthermia. All patients were regularly followed up within 6 months. Local control, complications, and survival were assessed. Materials included 156 patients with head and neck cancers treated palliatively with HDRBT and PDRBT in the Department of Otolaryngology of Poznań University of Medical Sciences and in the Department of Brachytherapy of Greater Poland Cancer Center from January 2002 to November 2008. RESULTS Complete and partial remissions 6 months after finishing the treatment were achieved in 37.7% of patients, whereas survival rates 12 and 24 months after brachytherapy were estimated for 40% and 17%, respectively. The overall complications rate was 35%. CONCLUSIONS Our results suggest that HDRBT and PDRBT constitute a safe alternative in the palliative treatment of patients with locally or regionally recurrent head and neck cancers with a relapse in a previously irradiated area, which were not qualified or rejected surgery. It gives a good palliative effect with acceptable complication rate.

HDR endobronchial brachytherapy (HDRBT) in the management of advanced lung cancer – Comparison of two different dose schedules

PURPOSE The aim of this work is to compare the results of various treatment protocols used in palliative HDRBT with the view of analyzing differences in survival and diminishing breathing difficulties. MATERIAL AND METHODS A total of 648 patients with advanced lung cancer were divided into two groups according to their clinical stage and the Zubrod-ECOG-WHO score. 303 (46.8%) patients received a total dose of 22.5 Gy in 3 fractions once a week, and 345 (53.2%) patients received a single fraction of 10 Gy. They were under clinical and endobronchial observation taking into consideration survival rates, local remission and duration of symptom relief such as dyspnoea, breathing, cough and haemoptysis. RESULTS There was no difference in the length of survival time between the two groups of patients (log-rank test, p=0.055). Patients showing improvement (objective response) survived longer than those who showed no change or progression (F Cox, p=0.000001). In multivariate analysis the other statistically important prognostic factors were: clinical stage of primary tumor (F Cox, p=0.000002), Zubrod-ECOG-WHO score (F Cox, p=0.002) and age of patients (F Cox, p=0.004). CONCLUSIONS The two treatment protocols showed similar efficiency in overcoming difficulties in breathing. Prognostic factors that significantly correlated with survival length were: grade of remission after treatment, clinical stage and performance status.

Benefit of Whole Pelvic Radiotherapy Combined with Neoadjuvant Androgen Deprivation for the High-Risk Prostate Cancer

Aim. To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. Material and Methods. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. Results. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. Conclusions. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.

Brachytherapy in accelerated partial breast irradiation (APBI) - review of treatment methods.

Breast conserving surgery (BCS) with following radiotherapy (EBRT) of the conserved breast became widely accepted in the last decades as the treatment of early invasive breast cancer. In an early stage of breast cancer, research has shown that the area requiring radiation treatment to prevent cancer from local recurrence is the breast tissue that surrounds the area where the initial cancer was removed. Accelerated partial breast irradiation (APBI) is an approach that treats only the lumpectomy bed with 1-2 cm margin, rather than the whole breast and as a result allows accelerated delivery of the radiation dose in four to five days. Published results of APBI are very promising. It is evident that APBI will play a role in the management of a selected group of early breast cancer. We discuss current status, indications, technical aspects and recently published results of APBI using different brachytherapy techniques.

GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update – Improvement by cross sectional imaging based treatment planning and stepping source technology

The Head and Neck Working Group of the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) published in 2009 the consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy in head & neck cancers. The use of brachytherapy in combination with external beam radiotherapy and/or surgery was also covered as well as the use of brachytherapy in previously irradiated patients. Given the developments in the field, these recommendations needed to be updated to reflect up-to-date knowledge. The present update does not repeat basic knowledge which was published in the first recommendation but covers in a general part developments in (1) dose and fractionation, (2) aspects of treatment selection for brachytherapy alone versus combined BT+EBRT and (3) quality assurance issues. Detailed expert committee opinion intends to help the clinical practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial cancers. Different aspects of adjuvant treatment techniques and their results are discussed, as well the possibilities of salvage brachytherapy applications.

Permanent implants in treatment of prostate cancer

Summary Low-dose rate brachytherapy (LDR – BT) is one of the radiation methods that is known for several years in treatment of localized prostate cancer. The main idea of this method is to implant small radioactive seeds as a source of radiation, directly into the prostate gland. LDR brachytherapy is applied as a monotherapy and also used along with external beam radiation therapy (EBRT) as a boost. In most cases it is used as a sole radical treatment modality, however not as a palliative treatment. The application of permanent seeds implants is a curative treatment alternative in patients with organ-confined cancer, without extracapsular extension of the tumour. Nowadays three kinds of radionuclide (I-125, Pd-103, Cs-131) are in use worldwide. This technique is particular favorite in United States, in Europe however, high-dose rate brachytherapy method (HDR BT) is more popular in early staged prostate cancer treatment (as a boost). HDR-BT monotherapy for early stage prostate cancer is still an investigational treatment. As monotherapy LDR-BT seems to be a reliable choice for early stage prostate cancer, according to low morbidity rate good results and short hospitalization. It is curative alternative of radical prostatectomy or external beam radiation (i.e. 3D CRT, IMRT) with comparable long-term survival and biochemical control and most favorable toxicity. The aim of this publication is to describe methods, indications, complications and selected results of prostate cancer LDR brachytherapy.

Brachytherapy in the treatment of lung cancer – a valuable solution

The majority of patients with lung cancer are diagnosed with clinically advanced disease. Many of these patients have a short life expectancy and are treated with palliative aim. Because of uncontrolled local or recurrent disease, patients may have significant symptoms such as: cough, dyspnea, hemoptysis, obstructive pneumonia, or atelectasis. Brachytherapy is one of the most efficient methods in overcoming difficulties in breathing that is caused by endobronchial obstruction in palliative treatment of bronchus cancer. Efforts to relieve this obstructive process are worthwhile, because patients may experience improved quality of their life (QoL). Brachytherapy plays a limited but specific role in definitive treatment with curative intent in selected cases of early endobronchial disease as well as in the postoperative treatment of small residual peribronchial disease. Depending on the location of the lesion, in some cases brachytherapy is a treatment of choice. This option is fast, inexpensive, and easy to perform on an outpatient basis. Clinical indications, different techniques, results, and complications are presented in this work.