Using HPLC for the determination of platinum drugs in biological matrixes after derivatization with diethyldithiocarbamate.

Challenges and pitfalls in the application of diethyldithiocarbamate derivatization for LC analysis of cisplatin and oxaliplatin, as well as the suitability of this method for different biological matrices with implications for use in routine practice have been identified. The LC of platinum drugs presents a significant challenge. They are polar compounds with poor retention on reverse phase packings. Cisplatin also exhibits poor absorption in UV and ionization in mass spectrometry. Therefore, we developed and optimized a derivatization approach for the LC analysis of total platinum in plasma, plasma ultrafiltrate, peritoneal fluid, and urine. Derivatization in urine proved to be difficult due to the complexity of the matrix, and extended testing was required. Our results highlight the important issues affecting the efficiency, reliability, and suitability of platinum drug derivatization. Although precolumn derivatization is less selective than its postcolumn counterpart, the application of precolumn derivatization is a simple, rapid, and universal approach for the determination of platinum drugs by HPLC. One of its major advantages is that it allows a more affordable analysis using UV detection without the need for additional high-end instrumentation such as a MS detector.

Non-Genomic Hallmarks of Aging-The Review.

Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis.

Total body irradiation for standard treatment rooms: a robust sweeping beam technique with respect to the body shape.

Background: The purpose of this work is to improve a sweeping beam technique for total body irradiation (TBI) on a low flat couch using a varying patient thickness model. We designed a flat couch for total body irradiation in supine and prone position. Three generic arcs with rectangular segments for a patient torso thickness of 16, 22 and 28 cm were generated with respect to varying patient thickness of four particular parts of the body: head, torso, thighs and calves. Materials and methods: Longitudinal and transversal dose profiles were measured using an ionization chamber and the EBT3 gafchromic film in a solid water slab phantom. The robustness of the method was examined in phantoms of different thicknesses. Results: Measured dose homogeneity stays within ±10% of prescribed dose for all of the three patient thickness models. The robustness of the method was evaluated as the increase in dose in the phantom center of 0.7% per 1 cm reduction in phantom thickness. Conclusion: The method is applicable for the broad range of patient sizes, comfortable for patients, robust and suitable for standard treatment rooms with a standard linear accelerator. It requires minimal investments into equipment.

Consensus recommendations from the Czech Head and Neck Cancer Cooperative Group (2019): definition of surgical margins status, neck dissection reporting, and HPV/p16 status assessment.

The Czech Head and Neck Cancer Cooperative Group (CHNCCG) held a meeting in Tabor on 11-12 October 2019 with the aim of reaching an interdisciplinary consensus on some controversial points where international unity is absent. The meeting resulted in recommendations on resection margin size terminology (definition of terms: negative margin, close margin and positive margin) and on the adoption of terminology for neck dissections reporting according to the International Recommendation of the International Head and Neck Scientific Group and on assessment of HPV/p16 status in head and neck tumors.

Cardiotoxicity of radiation therapy in esophageal cancer.

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data.

Validation of dose distribution computation on sCT images generated from MRI scans by Philips MRCAT.

AIM: To evaluate calculation of treatment plans based on synthetic-CT (sCT) images generated from MRI. BACKGROUND: Because of better soft tissue contrast, MR images are used in addition to CT images for radiotherapy planning. However, registration of CT and MR images or repositioning between scanning sessions introduce systematic errors, hence suggestions for MRI-only therapy. The lack of information on electron density necessary for dose calculation leads to sCT (synthetic CT) generation. This work presents a comparison of dose distribution calculated on standard CT and sCT. MATERIALS AND METHODS: 10 prostate patients were included in this study. CT and MR images were collected for each patient and then water equivalent (WE) and MRCAT images were generated. The radiation plans were optimized on CT and then recalculated on MRCAT and WE data. 2D gamma analysis was also performed. RESULTS: The mean differences in the majority of investigated DVH points were in order of 1% up to 10%, including both MRCAT and WE dose distributions. Mean gamma pass for acceptance criteria 1%/1 mm were greater than 82.5%. Prescribed doses for target volumes and acceptable doses for organs at risk were met in almost all cases. CONCLUSIONS: The dose calculation accuracy on MRCAT was not significantly compromised in the majority of clinical relevant DVH points. The introduction of MRCAT into practise would eliminate systematic errors, increase patients' comfort and reduce treatment expenses. Institutions interested in MRCAT commissioning must, however, consider changes to established workflow.

Neoadjuvant chemoradiotherapy of rectal carcinoma : Baseline hematologic parameters influencing outcomes.

BACKGROUND: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). RESULTS: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01-1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). CONCLUSION: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

Carrier molecules and extraction of circulating tumor DNA for next generation sequencing in colorectal cancer.

The aims of the study were: i) to compare circulating tumor DNA (ctDNA) yields obtained by different manual extraction procedures, ii) to evaluate the addition of various carrier molecules into the plasma to improve ctDNA extraction recovery, and iii) to use next generation sequencing (NGS) technology to analyze KRAS, BRAF, and NRAS somatic mutations in ctDNA from patients with metastatic colorectal cancer. Venous blood was obtained from patients who suffered from metastatic colorectal carcinoma. For plasma ctDNA extraction, the following carriers were tested: carrier RNA, polyadenylic acid, glycogen, linear acrylamide, yeast tRNA, salmon sperm DNA, and herring sperm DNA. Each extract was characterized by quantitative real-time PCR and next generation sequencing. The addition of polyadenylic acid had a significant positive effect on the amount of ctDNA eluted. The sequencing data revealed five cases of ctDNA mutated in KRAS and one patient with a BRAF mutation. An agreement of 86% was found between tumor tissues and ctDNA. Testing somatic mutations in ctDNA seems to be a promising tool to monitor dynamically changing genotypes of tumor cells circulating in the body. The optimized process of ctDNA extraction should help to obtain more reliable sequencing data in patients with metastatic colorectal cancer.

The Role of Adjuvant Radiotherapy in the Treatment of Breast Cancer.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

Tissue contexture determines the pattern and density of tumor-infiltrating immune cells in HPV-associated squamous cell carcinomas of oropharynx and uterine cervix.

The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.

Utilization of cone beam CT for reconstruction of dose distribution delivered in image-guided radiotherapy of prostate carcinoma - bony landmark setup compared to fiducial markers setup.

The purpose of this study was to compare two different styles of prostate IGRT: bony landmark (BL) setup vs. fiducial markers (FM) setup. Twenty-nine prostate patients were treated with daily BL setup and 30 patients with daily FM setup. Delivered dose distribution was reconstructed on cone-beam CT (CBCT) acquired once a week immediately after the alignment. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed 1 cm safety margin. Alternative plans assuming smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with initial ones. While the margin reduction in case of BL setup makes the prostate coverage significantly worse (p = 0.0003, McNemar's test), in case of FM setup with the reduced 7 mm margin, the prostate coverage is even better compared to BL setup with 10 mm margin (p = 0.049, Fisher's exact test). Moreover, partial volumes of organs at risk irradiated with a specific dose can be significantly lowered (p < 0.0001, unpaired t-test). Reducing of safety margin is not acceptable in case of BL setup, while the margin can be lowered from 10 mm to 7 mm in case of FM setup.

High-dose-rate brachytherapy at 3 Gy per fraction for lip carcinoma: Treatment outcomes and toxicity at 5-years.

PURPOSE: Low-dose-rate brachytherapy (LDR-BT) is a well-established treatment for lip cancer. High-dose-rate (HDR)-BT is a promising alternative to LDR-BT, but data are limited. In this context, we retrospectively evaluated treatment outcomes in a series of patients who underwent HDR-BT for lip carcinoma between 2003 and 2021. MATERIALS AND METHODS: A total of 32 patients were included in this study, with a median age of 73.5 years (range, 61 - 88). The indications for HDR-BT were as follows: primary treatment (n = 17), adjuvant treatment (n = 3), and recurrent disease after surgery (n = 12). The prescribed dose was 18 fractions of 3 Gy administered twice daily. RESULTS: At a median followup of 45 months (range, 12 -232), the 5-year local recurrence-free interval was 96.9% (95% CI: 90.9-100%), the disease-free interval was 85% (95% CI: 70.9-99.1), and 5-year overall survival was 64.7% (95% CI: 44.7-84.8). Eleven patients died, all on age related comorbidities. Acute toxicity manifested as G1 dry desquamation in 6 patients (18.8%), G2 erythema in 10 patients (31.2%) and G3 confluent moist desquamation in 16 patients (50%). Late complications included G1 fibrosis (100% of cases). G1 and G2 depigmentation was observed in 8 (25%) and 6 (18%) patients, G1 telangiectasia occurred in 5 patients (16%). CONCLUSIONS: These data support the use of HDR-BT for lip cancer. The dose and fractionation schedule used in this study (18 fractions x 3 Gy twice daily) seems to be effective and safe.

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

AIM: To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. BACKGROUND: Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. MATERIALS AND METHODS: Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. RESULTS: In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. CONCLUSION: Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

Is There Still a Place for Brachytherapy in the Modern Treatment of Early-Stage Oral Cancer?

Brachytherapy (BT) involves the direct application of radioactive sources to the tumour. This technique is characterised by a steep dose gradient, the delivery of high-dose radiation to the target volume centre, and the sparing of surrounding healthy tissues. Low-dose-rate (LDR) BT and manual afterloading played an important role in the treatment of early-stage oral cancer, with treatment outcomes that were comparable to surgery. Interest in BT as a primary treatment for oral cancer has declined in recent years due to the emergence of better surgical techniques, the switch from LDR BT to high-dose-rate (HDR) BT (which has a higher risk of complications), and to advances in external beam radiotherapy (EBRT). At present, the main indications for BT are in the postoperative setting due to the superior dose conformity and better quality of life offered by BT versus EBRT. Postoperative BT can be administered as monotherapy in early-stage (T1N0) cancers and in combination with elective neck dissection or EBRT to treat larger or deeper tumours. BT yields excellent results for lip carcinoma in older patients and in tumours with unfavourable localisations. BT is an effective salvage therapy for local recurrences in previously-irradiated areas. Despite its many advantages, brachytherapy is a complex treatment requiring meticulous technique and close cooperation between the radiation oncologist, physicist, and surgeon.

DNA hypermethylation of CADM1, PAX5, WT1, RARß, and PAX6 genes in oropharyngeal cancer associated with human papillomavirus.

Recently, an increasing incidence of HPV-induced oropharyngeal squamous cell carcinoma (OPSCC) has been observed. Moreover, locoregionally advanced stages require a combined modal approach, and the prognosis is poor. Therefore, it is essential to find early diagnostic and prognostic biomarkers. DNA methylation changes play a crucial role in the process of carcinogenesis and are often investigated as promising biomarkers in many types of cancer. For analysis of DNA methylation levels of selected tumour suppressor genes in HPV-positive and HPV-negative samples (including primary tumours and corresponding metastases of metastasizing OPSCCs, primary tumours of non-metastasizing OPSCCs, and control samples), methylation-specific MLPA and methylation-specific high-resolution melting analyses were used. A significant difference in methylation between OPSCCs and the control group was observed in WT1, PAX6 (P < 0.01) and CADM1, RARß (P < 0.05) genes. CADM1 and WT1 hypermethylation was detected mostly in HPV-positive samples; all but one HPV-negative samples were unmethylated. Moreover, hypermethylation of PAX5 gene was observed in metastases compared with control samples and was also associated with shorter overall survival of all patients (P < 0.05). Associations described herein between promoter methylation of selected genes and clinicopathological data could benefit OPSCC patients in the future by improvement in screening, early detection, and prognosis of the disease.

Special Techniques of Adjuvant Breast Carcinoma Radiotherapy.

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5-7 weeks of daily treatments, has been reduced to 3-4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.

High-Dose-Rate Brachytherapy as an Organ-Sparing Treatment for Early Penile Cancer.

BACKGROUND: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. METHODS: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. RESULTS: The median follow-up was 117.5 months (range, 5-210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7-97.7%) and 68.3% (95% CI: 44.0-92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45-97.7%) and 62.1% (95% CI: 34.8-89.4%), respectively. CONCLUSIONS: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort-the second largest reported to date in this clinical setting-prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer.

Establishment of a virtual transborder tumor board for cancer patients in Central and Southeastern Europe : An initiative of the Central European Cooperative Oncology Group (CECOG).

PURPOSE: To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE). METHODS: We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment. RESULTS: A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%). CONCLUSION: When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV­2 (severe acute respiratory syndrome coronavirus type 2) pandemic.

Analysis of D1853N ATM polymorphism in radiosensitive patients with cervical carcinoma.

UNLABELLED: Clinical oncologists have been focusing their efforts on attempting to define risk groups of patients with unusual biological reactions to the recommended therapy regimens using molecular biology techniques. THE AIMS OF OUR STUDY WERE: (i) to find a design and validate a method for fast and reliable analysis of the D1853N (5557G>A) genetic polymorphism in the ATM (ataxia-telangiectasia mutated) gene; (ii) to use side-directed mutagenesis to generate ATM 5557A-positive DNA (reference ATM5557A DNA); and (iii) to analyze a group of patients suffering from cervical carcinoma with adverse responses to radiotherapy. The 5557A variant was found in three of twenty women (15%). Our data show that the prevalence of the 5557A allelic variant in cervical cancer subjects with adverse responses after irradiation probably does not differ from the prevalence common in Caucasians. A larger population study should confirm these preliminary results.

Hyperfractionated high-dose rate brachytherapy in the treatment of oral tongue cancer.

BACKGROUND: Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results. AIM: The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily. PATIENTS AND METHODS: Twenty patients with squamous cell tongue cancer were treated in the years 2001-2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8-118) since brachytherapy. RESULTS: The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases. CONCLUSION: It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.