Pre-operative high-dose-rate brachytherapy in early-stage cervical cancer: long-term single-center results.

PURPOSE: The aim of the study was to report the outcomes of pre-operative high-dose-rate brachytherapy (pHDR-BT), followed by hysterectomy in patients with early cervical cancer. MATERIAL AND METHODS: From January, 1998 to December, 2003, 113 women with IB1, IB2, and IIA1 cervical cancer (according to International Federation of Gynecology and Obstetrics [FIGO] 2018) were treated with pHDR-BT, and 6 to 8 weeks later followed by radical hysterectomy. Patients found to have positive lymph nodes, residual cervical cancer, involved parametria, or lymphovascular space invasion (LVSI) received post-operative adjuvant therapy. RESULTS: Post-operatively, 81.4% of patients had a complete response to pHDR-BT in the cervix, and 18.6% had residual cervical cancer. Failures occurred in 11/113 (9.7%) patients (all were stage IIA1), with pelvic recurrences in 5/113 (4.4%) and distant metastasis (DM) in 6/113 (5.3%). The 5- and 10-year disease-free survival (DFS) rates were 100% for IB1 and IB2, and 86.4% and 81.3% for IIA1, respectively. Lymph node involvement and/or residual cervical cancer correlated with worse DFS. Two vesicovaginal fistulas were observed (one in a patient treated only with pHDR-BT and one in a woman, who underwent adjuvant external-beam radiotherapy [EBRT]). Two rectovaginal fistulas and one case of proctitis were observed in patients treated with adjuvant EBRT. CONCLUSIONS: pHDR-BT in early cervical cancer is well-tolerated and effective in sterilizing tumor cells in the cervix. The growing number of publications in this area may help define an optimal therapeutic scheme, but randomized trials are required to determine the best candidates for this treatment modality.In our opinion, cervical cancer patients with FIGO stage IIA1 are not good candidates for pHDR-BT, and could be given this treatment only after rigorous selection, including assessment with state-of-the-art imaging, due to higher probability of treatment failure.

Physical parameters in thermal imaging of basal cell cancer patients treated with high-dose-rate brachytherapy - first study.

Background: The basal cell carcinoma (BCC) is often treated by surgery or radiotherapy using ionizing radiation. While there is an established diagnostic path before treatment and also for the follow-up there are no good noninvasive methods objectifying irradiated area evolution during treatment. The main goal of preliminary studies was to try to answer if there are any useful information that can be derived from temperature effects of high-dose-rate (HDR) brachytherapy in treatment of BCC. Moreover, the temperature gradient was introduced as a physical parameter characterizing the thermal map of the lesion, its surroundings and reference area, which provided information about cancer tissue thermal reaction to brachytherapy. Materials and methods: Thirty-three patients suffering from BCC were monitored with thermovision during the brachytherapy treatment. All lesions were diagnosed as superficial and were confirmed with histopathology examination. Results: Results of the study showed two groups of patients characterized with two thermal maps and temperature gradient describing the lesion and surrounding area of BCC. The first group was characterized by higher temperature of the lesion than the surrounding tissue temperature (mean dT = 0,41°) whereas the other one, with lower lesion temperature (mean dT = -0.42°). It seems that the temperature changes observed in designated areas before and after therapy may provide physicians with additional information which could be useful in planning the treatment process, especially when considering temperature gradient changes during therapy. Conclusions: Although the data obtained indicate the possibilities of temperature distribution in pre-irradiation cases, further research is required for estimation of clinical effects of treatment.

Advanced dose calculation algorithm in superficial brachytherapy - the impact of tissue inhomogeneity on treatment plan dosimetry.

PURPOSE: Given tissue inhomogeneity and lack of backscatter media, superficial brachytherapy necessitates more accurate dosimetry than TG-43 formalism. However, the introduction of modern model-based dose calculation algorithms into clinical practice should be carefully evaluated. The aim of this work was to compare dose distributions calculated with TG-43 and advanced collapsed cone engine (ACE) algorithms for individual multi-catheter moulds, and investigate the impact of target size and the lack of bolus to differences between plans. MATERIAL AND METHODS: Eleven treatment plans for individual mould multi-catheter high-dose-rate brachytherapy (IMM HDR) were selected for retrospective analysis. All treatment plans were initially calculated with TG-43 formula and re-calculated using ACE algorithm. Plan re-calculation with ACE was repeated for each plan in order to assess the impact of bolus. To evaluate differences between TG-43 and ACE dose distributions, dose-volume histogram (DVH) parameters for each ROI were compared. Dmax (maximal point dose), D0.1cc, and D2cc were calculated for each risk's organ (OARs) and for external contour. For clinical target volume (CTV), D98, D90, D50, CTV coverage (CTV-V100), and dose delivered to reference point were compared between the plans. RESULTS: A significantly lower values (p < 0.05) of CTV parameters were observed for treatment plans calculated with ACE algorithm comparing to TG-43. Further analysis showed that differences between CTV-V100 for ACE and TG-43 plans depended on CTV volume. Dosimetric parameters for OARs were significantly lower in ACE plans than those of TG-43. Only D2cc for external and D0.1cc for both eye lenses in ACE plans were insignificantly different comparing to TG-43 plans. CONCLUSIONS: Results show that differences between dosimetric parameters are statistically significant. However, their clinical relevance is still undetermined. Careful re-evaluation of the clinical results based on long-term research on TG-43 is necessary to safely introduce modern algorithms to clinical practice.

Individual multi-catheter mould technique in high-dose-rate brachytherapy - personalized approach in treating multifocal angiosarcoma of the face.

PURPOSE: The aim of this study was to report individual surface mould multi-catheter high-dose-rate (IMM HDR) application as a salvage treatment for a head and neck angiosarcoma patient, previously treated with surgery followed by external beam radiotherapy. MATERIAL AND METHODS: A 74-year-old male reported to our center with an uncommon malignant neoplasm of blood vessels. The patient was qualified for a wide local excision (WLE) of tumor with simultaneous reconstruction using a free-flap collected from the patient's thigh. After surgery, the patient was qualified for adjuvant external-beam radiotherapy (EBRT). Volumetric arc therapy (VMAT; RapidArc®, Varian Medical Systems) was used to deliver 52.8 Gy/1.6 Gy in 33 fractions. Overall treatment time was 51 days. Six months after radiotherapy, an incisional biopsy of non-healing ulcer of the nasal bridge revealed angiosarcoma. Wide local excision with skin graft reconstruction was planned. Due to multifocal disease and lack of possibility for further margin, the resection surgery was completed after skin graft reconstruction from the right thigh. Surface IMM HDR was considered as an alternative option for further treatment. Total dose of 48 Gy (12 fractions) was planned. RESULTS: One month after surface IMM HDR, healing process of the skin was observed in the treated regions and six months later, the irradiated areas recovered. General condition of the patient deteriorated two years after diagnosis and one year after HDR. He was hospitalized to receive palliative care. CONCLUSIONS: HDR brachytherapy may be a valuable option for angiosarcoma treatment. Difficult lesion location may yield non-radical surgery. Surface IMM HDR provides highly conformal plan and allow adjusting the dose to individual clinical situation.

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy.

PURPOSE: To report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution. METHODS: Seventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3-3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4-7 Gy given once or twice a week). RESULTS: Median follow-up was 76 months (7-204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9-54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation. CONCLUSIONS: HDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.

Salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after primary radiotherapy failure.

BACKGROUND AND PURPOSE: To evaluate high-dose-rate brachytherapy (HDR BT) as a salvage modality for locally recurrent prostate cancer after primary radiotherapy failure. MATERIALS AND METHODS: Eighty-three prostate cancer patients, who locally relapsed after radiotherapy, were treated with salvage HDR BT. The schedule was three implantations, every two weeks, with 10Gy per implant, to a total dose of 30Gy. Acute and late toxicity rates were evaluated. Overall survival (OS) and biochemical control were calculated using Kaplan-Meier method. RESULTS: Median follow-up after salvage HDR was 41months. The 3-year and 5-year OS were 93% and 86%, respectively. The 3-year and 5-year biochemical disease-free survival (bDFS) were 76% and 67%, respectively. The single factor associated with biochemical control was time to achieve salvage PSA nadir (p-.006). OS was linked significantly with primary nadir level (p-.001) while primary biochemical relapse interval was of borderline significance (p-.07). CONCLUSIONS: Salvage HDR BT is a promising treatment option for patients with localized relapse of previously irradiated prostate cancer. Lower PSA nadir after primary radiotherapy and longer primary disease-free interval influence the outcome.

Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer.

PURPOSE: The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. MATERIAL AND METHODS: Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). RESULTS: Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). CONCLUSIONS: High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This hypothesis should be verified in a larger group of patients.

Proposal of thermal imaging application in photodynamic therapy-Preliminary report.

There are many different skin lesions that manifest a skin temperature gradient. Basal cell carcinoma (BCC) is the most frequently occurring type of malignant skin lesion (almost 95% of all skin tumors). BCC is sometimes treated by using photodynamic therapy which is very well tolerated by patients and provides good results, especially in superficial skin layer lesions. The results of our studies showed significant changes in the area of temperature gradient due to photodynamic therapy. It seems that the ability to acquire knowledge of such area changes may provide additional useful information to physicians. The increase of observed isotherm area in comparison to lesion size on the skin was a few times higher. It may suggest the range of areas where the metabolism processes take place. Due to the accumulation of photosensitivity only in tumor cells, we theorize that such a large region of increased metabolism observed during therapy may be connected with a larger range of tumor cells than was previously predicted through diagnosis. However, it should be noted that the region can be much bigger due to the existing heat transfer. The results obtained have a potential meaning in describing the range of chemical and physiological processes occurring during photodynamic therapy.

The importance of the implant quality in APBI - Gliwice experience. Dosimetric evaluation.

This study includes four years of our clinical trials to improve implant quality in multicatheter accelerated partial breast irradiation (APBI). The progress in dosimetric and volumetric parameters of the treatment plans was evaluated. One hundred and ninety-one women, for whom treatment plans were made based on three dimensional imaging, were selected for the study. To evaluate progress made in our APBI procedure, following parameters and indices were taken into account: percentage of the target volume receiving the reference dose (PTVref), minimum dose in the target volume expressed as a percentage of reference dose (PTVmin), dose homogeneity index (DHI), and conformity index (COIN). Additionally, the plan quality index was calculated for every group as the sum of mean values of four evaluated parameters. PTVref have increased from the mean value of 83.4% at the beginning to recent 94.8%. The maximum value equals to 95.4%. The same trend can be observed with PTVmin value, which has been improved from 51.7% to 70.1%, maximally. DHI and COIN mean values present similar progress. DHI value increased from 0.53 level to 0.68, and COIN from 0.58 in 2009 to 0.74. Plan quality index has increased from 2.46 in 2009 to 3.06, recently. The implant quality is crucial for the accurate dose distribution. This paper shows the progress that was made in APBI procedure to improve implant quality. Nowadays, our implant technique is based on three-dimensional CT imaging results in acceptable dose distributions.

Interstitial HDR brachytherapy (HDR-BT) in early stage mobile tongue cancers in young patients - Gliwice experience.

PURPOSE: In early stage mobile tongue cancer radical radiotherapy offers good local control and organ preservation, which is especially important in the group of young patients. In our department, for many years HDR-BT has been performed in mobile tongue cancers as a sole treatment or as a "boost" with EBRT. The aim of the study was to show our experience with HDR-BT in early stage mobile tongue cancers among young patients. MATERIAL AND METHODS: From 2001 to 2006 in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, five patients under 45 years with mobile tongue cancer were treated with HDR brachytherapy (T1N0M0 - 3/5 and T2N0M0 - 2/5); 4 with HDR brachytherapy "boost" and 1 as a sole treatment. One woman was previously treated with tumour resection, but because of positive surgical margins was referred for radiotherapy. All patients had clinically negative lymph nodes, without dissection. They were treated with interstitial HDR-BT (3-8 catheters). In 4 patients treated with HDR-BT as a "boost", total doses ranged from 18 to 21 Gy given in 6-7 fractions (twice a day, 3 Gy per fraction). Total doses in EBRT (to local lymph nodes and tumour bed) ranged from 50 to 60 Gy (1.8-2 Gy per fraction 5 days/week). One patient, treated with radical HDR brachytherapy, received 45 Gy in 10 fractions and 50 Gy in EBRT to regional lymph nodes. RESULTS: We did not notice local recurrences or distant metastases in our group of patients. Median follow-up was 67 months (range 47-79 months). All patients preserved normal tongue function. A severe late complication occurred in 1 patient - fracture of the mandible. CONCLUSIONS: In the analysed group of young patients with mobile tongue cancer interstitial HDR brachytherapy in combination with EBRT was an effective and well tolerated treatment modality which allowed preservation of the tongue and its function.

Comparison of 2D- and 3D-guided implantation in accelerated partial breast irradiation (APBI).

PURPOSE: In this study two different pre-planning methods (2D vs. 3D) were compared in respect to the implant quality as judged by volumetric and dose parameters of the treatment plans. The aim of this work was to evaluate the influence of the imaging modalities used for pre-planning purpose to the treatment plan quality. MATERIAL AND METHODS: Twenty-four patients treated with HDR multicatheter implants were randomly selected for experiment. All patients underwent breast conserving surgery. Flexible catheters were implanted into the breast through the template. Inter-catheter distance, number of planes and catheters were adjusted, in respect to the size and location of the target. Pre-planning was used to evaluate the implant geometry in respect to the target. Needles number and position were modified if necessary. There were two experimental subgroups consisted of 12 patients each. Different pre-planning procedure was employed in each group. In the first group 2D X-ray imaging system was used. In the second one the 3D pre-planning method based on CT was performed. Treatment plans were evaluated with parameters calculated based on dose-volume histograms (DVHs). Volumetric and dose parameters were used for comparison of the dose distribution between the two experimental subgroups. RESULTS: The mean value of target coverage VPTV100 is higher for 3D pre-planning than for 2D (91.7% vs. 86.1%). The dose that covers 90% of the PTV (D90) is also higher for 3D pre-planning than for 2D (4.2 Gy vs. 3.6 Gy). Similar relation can be observed for the values of dose homogeneity index where DHI obtained for 3D pre-planning is 0.60 and 0.53 for 2D. All differences were statistically significant with p < 0.05. CONCLUSIONS: Analysis presented in this paper showed that 3D pre-planning method improves the geometrical quality of the implant.