Anna Bartochowska

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.

The role of high-dose-rate and pulsed-dose-rate brachytherapy in the management of recurrent or residual stomal tumor after total laryngectomy.

The main purpose of the study was to assess the role and efficacy of high‐dose‐rate (HDRBT) and pulsed‐dose‐rate (PDRBT) brachytherapy in the palliative treatment of recurrent or residual stomal tumor after total laryngectomy.

How to deal with laryngeal amyloidosis? Experience based on 16 cases

Introduction: Amyloidosis is characterized by the deposition of amorphous fibrillar protein (amyloid) in the intercellular or intracellular space. Localized amyloidosis is rare in the head and neck area. In Polish literature of the last decade it has been the subject of case studies. Aim: The goal of the study was to carry out a retrospective analysis of patients treated for amyloidosis in the Department of Otolaryngology and Head and Neck Surgery of the Poznań University of Medical Sciences in the period from 2000 to 2009. Based on the collected clinical material, the authors made an attempt to determine the most frequent anatomical location of amyloid deposits and the most frequently affected organs, the type and duration of symptoms, the therapeutic approach, further diagnostic measures taken and the final outcome of the treatment. The next goal was to assess the number of microlaryngoscopies performed in patients with amyloidosis affecting the larynx as compared to the overall number of such procedures. Material: The detailed analysis included 16 patients with laryngeal amyloidosis. Results: Amyloidosis of the larynx was found in only 0.52% of patients undergoing microlaryngoscopies in the period from 2000 to 2009. In the vast majority of patients (11 of 16), there was no suspicion of amyloidosis in the initial diagnosis. Only the histopathological assessment definitely confirmed the nature of pathological changes in the larynx. Glottis was the most common location of amyloid deposits in the study group. In all cases, additional studies and long-term monitoring of the postoperative course excluded generalized amyloidosis. Conclusions: Laryngeal amyloidosis is very rare, however it should be considered in the differential diagnosis in patients with laryngeal dysfunction. Surgery remains the treatment of choice in most patients, although the attempts of radiotherapy are undertaken. Preserving the normal function of the organ remains the priority.

Recurrent amplification in the 22q11 region in laryngeal squamous cell carcinoma results in overexpression of the CRKL but not the MAPK1 oncogene

Thirteen laryngeal squamous cell carcinoma cell lines were recently studied by array comparative genomic hybridization (array-CGH) in order to identify recurrent DNA copy number alterations in the tumor genome. A highly amplified region 22q11.2 was found in two of the thirteen cell lines. Two established oncogenes CRKL and MAPK1 are localized in this region, but only CRKL was amplified in both cell lines. Therefore, to check if amplification of either CRKL or MAPK1 genes may be important in the pathogenesis of laryngeal squamous cell carcinoma, the DNA copy number and mRNA expression were measured in a cohort of 17 LSCC cell lines by quantitative real-time PCR (qPCR). For the CRKL gene gains of the copy number were found in 3/17 cell lines, while overexpression was found in 6/17 cell lines. Gains in the copy number for the MAPK1 gene were found in 1/17 cell lines, but overexpression was not detected in any cell line. A highly significant correlation between DNA copy number and expression for CRKL gene, but not for MAPK1 gene was established using the Pearson test. Thereafter, 46 primary samples of laryngeal cancer were tested by qPCR to check for possible gains in copy number of the CRKL gene. Gains were found in 3/46 cases. These results suggest that CRKL, but not MAPK1 is the target oncogene of the rare but recurrent amplification at 22q11.2 in laryngeal squamous cell carcinoma.

Value of open horizontal glottectomy in the treatment for T1b glottic cancer with anterior commissure involvement.

The aim of the study was to evaluate the treatment outcomes in the group of 108 T1b glottic cancer patients with the anterior commissure involvement treated with open horizontal glottectomy and to compare them with transoral laser microsurgery (TLM) or primary radiotherapy (XRT) results from the literature review.

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.

Is there a place for brachytherapy in the salvage treatment of cervical lymph node metastases of head and neck cancers

PURPOSE Therapeutic options are limited for unresectable isolated cervical lymph node recurrences. The purpose of the study was to evaluate the feasibility, safety, and efficacy of high-dose-rate (HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) in such cases. METHODS AND MATERIALS Sixty patients have been analyzed. All them had previously been treated with radical radiotherapy or chemoradiotherapy with or without surgery. PDR-BT and HDR-BT were used in 49 and 11 patients, respectively. In PDR-BT, a dose per pulse of 0.6-0.8 Gy (median 0.7 Gy) was given up to a median total dose of 20 Gy (range, 20-40 Gy). HDR-BT delivered a median total dose of 24 Gy (range, 7-60 Gy) in 3-10 fractions at 3-6 Gy per fraction. RESULTS The overall survival and lymph node control rates at 1 and 2 years were estimated for 31.7% and 19%, and 41.4% and 27.3%, respectively. Serious late side effects (soft tissue necrosis) were observed in 11.7% of patients. Adverse events occurred statistically more often in patients >59 years (p = 0.02). CONCLUSIONS HDR-BT and PDR-BT are feasible in previously irradiated patients with isolated regional lymph node metastases of head and neck cancers. The techniques should be considered if surgery is contraindicated. They provide acceptable toxicity and better tumor control than chemotherapy alone.

Schemat postępowania i wstępne wyniki leczenia brodawczaków krtani dotkankowym preparatem cidofovir

Summary Introduction Recurrent respiratory papillomatosis (RRP) is a rare disease in children and adults. It is characterized by proliferation of benign squamous cell papillomas within the respiratory-digestive tract, predominantly the larynx. Standard treatment consists of surgical excision of papillomata to maintain airway patency and voice quality. For last several years cidofovir is the most contemporary adjuvant anti-viral treatment for recurrent respiratory papillomatosis and its topical use is widely described. Material and methods Intralesional cidofovir therapy was given to 20 patients treated for laryngeal papillomas in the Department of Otolaryngology in Poznan between I-XII.2009. The character of the lesion differed: from one anatomical site and moderate growth to four or five localizations with heavy extension. The number of cidofovir injections per patient varied from one to six times and the volume of solution ranges from 1–12 ml. The cidofovir injections were combined with laser or mechanical excision of the lesions. In disperse papillomata the injections administered in particular anatomical sites in 4–6 weeks period. In massive lesions injections were repeated in the same anatomical site. Results Complete remission was observed in 3 out of 20 patients. 12 patients show remission in a place of cidofovir injection. In 4 patients during the 4 week observation new foci of papillomatosis occurred. In two patients hepatic toxic side effect were observed. Conclusions Intralesional cidofovir injection has been shown to be an effective an safe therapy for laryngeal papilloma and should be considered in those patients who experienced disease relapse.

Recurrent epigenetic silencing of the PTPRD tumor suppressor in laryngeal squamous cell carcinoma

Cellular processes like differentiation, mitotic cycle, and cell growth are regulated by tyrosine kinases with known oncogenic potential and tyrosine phosphatases that downmodulate the first. Therefore, tyrosine phosphatases are recurrent targets of gene alterations in human carcinomas. We and others suggested recently a tumor suppressor function of the PTPRD tyrosine phosphatase and reported homozygous deletions of the PTPRD locus in laryngeal squamous cell carcinoma. In this study, we investigated other gene-inactivating mechanisms potentially targeting PTPRD, including loss-of-function mutations and also epigenetic alterations like promoter DNA hypermethylation. We sequenced the PTPRD gene in eight laryngeal squamous cell carcinoma cell lines but did not identify any inactivating mutations. In contrast, by bisulfite pyrosequencing of the gene promoter region, we identified significantly higher levels of methylation (p = 0.001 and p = 0.0002, respectively) in 9/14 (64%) laryngeal squamous cell carcinoma cell lines and 37/79 (47%) of primary laryngeal squamous cell carcinoma tumors as compared to normal epithelium of the upper aerodigestive tract. There was also a strong correlation (p = 0.0001) between methylation and transcriptional silencing for the PTPRD gene observed in a cohort of 497 head and neck tumors from The Cancer Genome Atlas dataset suggesting that DNA methylation is the main mechanism of PTPRD silencing in these tumors. In summary, our data provide further evidence of the high incidence of PTPRD inactivation in laryngeal squamous cell carcinoma. We suggest that deletions and loss-of-function mutations are responsible for PTPRD loss only in a fraction of cases, whereas DNA methylation is the dominating mechanism of PTPRD inactivation.

The Knowledge of the Role of Papillomavirus—Related Head and Neck Pathologies among General Practitioners, Otolaryngologists and Trainees. A Survey-Based Study

Objectives The aim of the survey was to introduce knowledge of HPVs role in head and neck pathologies to general physicians (GPs), otorhinolaryngologists (ENTs) and newly graduated doctors, as well as to promote HPV-related diseases prevention. Study Design Cross-sectional study. Methods Self-designed questionnaire was sent to 2100 doctors. A total of 404 doctors, including 144 ENTs, 192 GPs and 68 trainees, responded. Results The majority of ENTs (86.8%) had contact with recurrent respiratory papillomatosis (RRP) and oropharyngeal cancers (OPCs) patients; in contrast, the majority of GPs (55.7%) did not (p = 0.00). The knowledge of HPV aetiology of cervical cancer versus OPCs and RRP was statistically higher. 7% of ENTs, 20% of GPs and 10% of trainees had not heard about HPV in oropharyngeal diseases. Women had greater knowledge than men. Both in the group of GPs and ENTs, 100% of respondents had heard about the impact of vaccination on the reduction of cervical cancer incidence. Only 39.11% of respondents had heard about the possibility of using vaccination against HPV in RRP—ENT doctors significantly more often than GPs and trainees (p = 0.00). Only 28.96% of physicians had heard about the potential value of HPV vaccination in preventing OPCs, including 44.44% of ENT doctors, 23.44% of GPs and 11.76% of trainees (p = 0.00). The doctors from district hospitals showed lower level of knowledge compared with clinicians (p = 0.04). Conclusions The different levels of knowledge and awareness of HPV issues highlight the need for targeted awareness strategies in Poland with implementation of HPV testing and vaccination. The information should be accessible especially to those with lower education levels: ENTs from small, provincial wards, GPs from cities of < 200 000 inhabitants and older physicians. The incorporation of HPV issues into the studies curriculum would be fruitful in terms of improving the knowledge of trainees.