EZH2 Expression in Head-and-Neck Squamous Cell Cancer in Young Patients.

EZH2 (Enhancer of zeste homolog 2) promotes tumor growth and survival through numerous mechanisms and is a promising target for novel therapeutic approaches. We aimed to characterize the expression of EZH2 in the tumors of young head-and-neck squamous cell cancer (HNSCC) patients in comparison with the general HNSCC patient population. We used formalin-fixed, paraffin-embedded tissue blocks from 68 random young HNSCC patients (≤39 years, median age: 36 years; diagnosed between 2000 and 2018), which were compared with the samples of 58 age- and gender-matched general HNSCC subjects (median age: 62 years; all diagnosed in the year 2014). EZH2 and p53 expression of the tumors was detected using immunohistochemical staining. Lower EZH2 expression was found to be characteristic of the tumors of young HNSCC patients as opposed to the general population (median EZH2 staining intensity: 1 vs. 1.5 respectively, p < 0.001; median fraction of EZH2 positive tumor cells: 40% vs. 60%, respectively, p = 0.003, Mann-Whitney). Cox analysis identified a more advanced T status (T3-4 vs. T1-2), a positive nodal status, and alcohol consumption, but neither intratumoral EZH2 nor p53 were identified as predictors of mortality in the young patient group. The lower EZH2 expression of young HNSCC patients' tumors discourages speculations of a more malignant phenotype of early-onset tumors and suggests the dominant role of patient characteristics. Furthermore, our results might indicate the possibility of an altered efficacy of the novel anti-EZH2 therapies in this patient subgroup.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

BACKGROUND: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. METHODS: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. RESULTS: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. CONCLUSIONS: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.

Dosimetric comparison of postoperative interstitial high-dose-rate brachytherapy and modern external beam radiotherapy modalities in tongue and floor of the mouth tumours in terms of doses to critical organs.

BACKGROUND: The aim of the study was to dosimetrically compare interstitial high-dose-rate (HDR) brachytherapy (BT) and modern external beam radiotherapy modalities, as volumetric modulated arc therapy (VMAT) and stereotactic radiotherapy with Cyberknife (CK) of tumours of the tongue and floor of the mouth in terms of dose to the critical organs. PATIENTS AND METHODS: In National Institute of Oncology, Budapest, between March 2013 and August 2022 twenty patients (11 male/9 female) with stage T1-3N0M0 tongue (n = 14) and floor of mouth (n = 6) tumours received postoperative radiotherapy because of close/positive surgical margin and/or lymphovascular and/or perineural invasion. High-dose-rate interstitial brachytherapy applying flexible plastic catheters with a total dose of 15 × 3 Gy was used for treatment. In addition to BT plans VMAT and stereotactic CK plans were also made in all cases, using the same fractionation scheme and dose prescription. As for the organs at risk, the doses to the mandible, the ipsilateral and the contralateral salivary glands were compared. RESULTS: The mean volume of the planning target volume (PTV) was 12.5 cm3, 26.5 cm3 and 17.5 cm3 in BT, VMAT and CK techniques, respectively, due to different safety margin protocols. The dose to the mandible was the most favourable with BT, as for the salivary glands (parotid and submandibular) the CK technique resulted in the lowest dose. The highest dose to the critical organs was observed with the VMAT technique. The mean values of D2cm3 and D0.1cm3 for the critical organs were as follows for BT, VMAT and CK plans: 47.4% and 73.9%, 92.2% and 101.8%, 68.4% and 92.3% for the mandible, 4.8% and 6.7%, 7.3% and 13.8%, 2.3% and 5.1% for the ipsilateral parotid gland, 3.5% and 4.9%, 6.8% and 10.9%, 1.5% and 3.3% for the contralateral parotid gland, 7.3% and 9.4%, 9.0% and 14.3%, 3.6% and 5.6% for the contralateral submandibular gland. CONCLUSIONS: The present results confirm that BT, despite being an invasive technique, is dosimetrically clearly beneficial in the treatment of oral cavity tumours and is a modality worth considering when applying radiotherapy, not only as definitive treatment, but also postoperatively. The use of the CK in the head and neck region requires further investigation.

Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cervical nodes from CUP. The primary treatment was cervical node dissection ± radiotherapy. All patients had elevated (>1.0 chromatid break/cell) MS. One male patient died of progressive neck metastasis within 3 years and the 3 female patients are still alive more than 15 years after initial treatment of HPV+ (two) or cystic (one) SCC. Two female patients developed second and third distant site metachronous primary cancers. HPV+ or cystic HNSCC from CUP with elevated MS indicates good outcome. Distant site metachronous cancers of different histologic origins cannot be explained by field cancerization. The clinical significance of elevated MS in neck node SCC metastasis from CUP requires further investigation.

The characteristics of head and neck squamous cell cancer in young adults: A retrospective single-center study.

We aimed to characterize clinical and prognostical factors of primary head and neck squamous cell carcinoma (HNSCC) in 85 young patients (≤39 years, median age: 37 years; between 2000-2018) in comparison with 140 institutional general HNSCC patients (median age: 61.5 years). The patient's medical records were collected from the institutional database. The prevalence of smoking and alcohol consumption (65.8% and 48.1%) in the young group exceeded the regional population average but was below the institutional (86.4% and 55%) general HNSCC patient population. Primary tumor sites in the group of young patients were as follows: oral cavity (56.4%), oropharynx (17.6%), hypopharynx (11.7%), and larynx (14.1%). Cumulative five-year overall survival was 44.2% in the young group, but significantly better with early T (T1-2 vs. T3-4: 52.6% vs. 26.7%; p = 0.0058) and N0 status (N0 vs. N+: 65.2% vs. 32.3%; p = 0.0013). Young age, abstinence, earlier stage and laryngeal tumor site might predict a better prognosis. The age distribution and the high prevalence of traditional risk factors among the young patients as well as the predominance of oral cavity tumor localization suggest that the early onset of tumor development could be originated from the premature failure of the intrinsic protective mechanisms.

Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia.

BACKGROUND: FA patients are hypersensitive to preconditioning of bone marrow transplantation. OBJECTIVE: Assessment of the power of mitomycin C (MMC) test to assign FA patients. METHODS: We analysed 195 patients with hematological disorders using spontaneous and two types of chromosomal breakage tests (MMC and bleomycin). In case of presumed Ataxia telangiectasia (AT), patients' blood was irradiated in vitro to determine the radiosensitivity of the patients. RESULTS: Seven patients were diagnosed as having FA. The number of spontaneous chromosomal aberrations was significantly higher in FA patients than in aplastic anemia (AA) patients including chromatid breaks, exchanges, total aberrations, aberrant cells. MMC-induced ≥10 break/cell was 83.9 ± 11.4% in FA patients and 1.94 ± 0.41% in AA patients (p < .0001). The difference in bleomycin-induced breaks/cell was also significant: 2.01 ± 0.25 (FA) versus 1.30 ± 0.10 (AA) (p = .019). Seven patients showed increased radiation sensitivity. Both dicentric + ring, and total aberrations were significantly higher at 3 and 6 Gy compared to controls. CONCLUSIONS: MMC and Bleomycin tests together proved to be more informative than MMC test alone for the diagnostic classification of AA patients, while in vitro irradiation tests could help detect radiosensitive-as such, individuals with AT.

Are active dwell positions always necessary in the ring/ovoids channel of the cervical applicator in the intracavitary-interstitial brachytherapy of cervical cancer?

Purpose: To compare dosimetric parameters of brachytherapy (BT) treatment plans made with or without active source positions of the ring/ovoid (R/O) applicator in locally advanced cervical cancer patients. Material and methods: Sixty patients with cervical cancer without vaginal involvement were selected for the study, who received intra-cavitary/interstitial BT. For each patient, two plans with and without active source dwell positions in R/O were created, using the same dose-volume constraints. EQD2 total doses from external beam and BT of target volumes and organs at risk (OARs) between the competing plans were compared. Results: There was no significant difference in the dose of high-risk clinical target volume (HR-CTV) and gross tumor volume (GTV) between the plans with inactive vs. active R/O. The mean D98 of intermediate-risk clinical target volume (IR-CTV) was significantly lower with inactive R/O; however, the GEC-ESTRO (EMBRACE II study) and ABS criteria were fulfilled in 96% in both plans. There was no difference in dose homogeneity, but conformity of the plans with inactive R/O was higher. Doses to all OARs were significantly lower in plans without R/O activation. While all the plans without R/O activation fulfilled the recommended dose criteria for OARs, it was less achievable with R/O activation. Conclusions: Inactivation of R/O applicator results in similar dose coverage of the target volumes with lower doses to all OARs, as activation of R/O in cervix cancer patients when HR-CTV does not extend to R/O applicator. The use of active source positions in R/O shows worse performance regarding the fulfilment of the recommended criteria for OARs.

Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations.

BACKGROUND: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. METHODS: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. RESULTS: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. CONCLUSIONS: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system.

CyberKnife versus multicatheter interstitial brachytherapy for accelerated partial breast irradiation: a dosimetrical assessment with focus on organs at risk.

Background: The purpose of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation with special focus on dose to organs at risk (OARs). Materials and methods: Treatment plans of thirty-one patients treated with MIBT were selected and additional CK plans were created on the same CT images. The OARs included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left sided cases. The fractionation was identical (4 × 6.25 Gy). Dose-volume parameters were calculated for both techniques and compared. Results: The D90 of the PTV for MIBT and CK were similar (102.4% vs. 103.6%, p = 0.0654), but in COIN the MIBT achieved lower value (0.75 vs. 0.91, p < 0.001). Regarding the V100 parameter of non-target breast CK performed slightly better than MIBT (V100: 1.1% vs. 1.6%), but for V90, V50 and V25 MIBT resulted in less dose. Every examined parameter of ipsilateral lung, skin, ribs and contralateral lung was significantly smaller for MIBT than for CK. Protection of the heart was slightly better with MIBT, but only the difference of D2cm3 was statistically significant (17.3% vs. 20.4%, p = 0.0311). There were no significant differences among the dose-volume parameters of the contralateral breast. Conclusion: The target volume can be properly irradiated by both techniques with high conformity and similar dose to the OARs. MIBT provides more advantageous plans than CK, except for dose conformity and the dosimetry of the heart and contralateral breast. More studies are needed to analyze whether these dosimetrical findings have clinical significance.

Effect of a lead block on alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer: using model-based dose calculation algorithms to correct for inhomogeneity.

PURPOSE: The purpose of this study was to evaluate the effect of a lead block for alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer. MATERIAL AND METHODS: We treated 6 patients and delivered 5,400 cGy in 9 fractions using a lead block. Effects of lead block (median thickness, 4 mm) on dose attenuation by distance were visually examined using TG-43 formalism-based dose distribution curves to determine whether or not the area with the highest dose is located in the alveolar bone, where there is a high-risk of infection. Dose re-calculations were performed using TG-186 formalism with advanced collapsed cone engine (ACE) for inhomogeneity correction set to cortical bone density for the whole mandible and alveolar bone, water density for clinical target volume (CTV), air density for outside body and lead density, and silastic density for lead block and its' silicon replica, respectively. RESULTS: The highest dose was detected outside the alveolar bone in five of the six cases. For dose-volume histogram analysis, median minimum doses delivered per fraction to the 0.1 cm3 of alveolar bone (D0.1cm3 TG-43, ACE-silicon, and ACE-lead) were 344.3 (range, 262.9-427.4) cGy, 336.6 (253.3-425.0) cGy, and 169.7 (114.9-233.3) cGy, respectively. D0.1cm3 ACE-lead was significantly lower than other parameters. No significant difference was observed between CTV-related parameters. CONCLUSIONS: The results suggested that using a lead block for alveolar bone protection with a thickness of about 4 mm, can shift the highest dose area to non-alveolar regions. In addition, it reduced D0.1cm3 of alveolar bone to about half, without affecting tumor dose.

Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1-2 tongue tumours.

PURPOSE: To describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection. METHODS: Between January 1998 and April 2019, 45 patients with squamous cell histology, stage T1-2N0-1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10-45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed. RESULTS: During a mean follow-up of 103 months (range: 16-260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001). CONCLUSION: Sole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.

The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry.

Brachytherapy (BT) has long been used for successful treatment of various tumour entities, including prostate, breast and gynaecological cancer. However, particularly due to advances in modern external beam techniques such as intensity-modulated radiotherapy (IMRT), volume modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), there are concerns about its future. Based on a comprehensive literature review, this article aims to summarize the role of BT in cancer treatment and highlight its particular dosimetric advantages. The authors conclude that image-guided BT supported by inverse dose planning will successfully compete with high-tech EBRT in the future and continue to serve as a valuable modality for cancer treatment.

[Trimodal, organ-preserving treatment of organ-confined, muscle-invasive bladder cancer]. / Szervre lokalizált, izominvazív húgyhólyagrák trimodális, szervmegtartó kezelése.

Radical cystectomy is the gold standard treatment in localized muscle-invasive bladder cancer according to today's guidelines. However, in many cases, surgery is not possible due to the patient's general condition, or the patient refuses bladder removal. In such cases, as well as in some selected patients suitable for surgery, trimodal organ preservation therapy is an alternative, which provides the patient with similar survival, local tumor control, so that 80% of patients retain their bladder. In some cases, due to complications or a muscle-invasive local recurrence in the bladder, the bladder may not be retained. At this point, a salvage cystectomy can still save the patient's quality of life and life. Adequate patient selection is a prerequisite for effective trimodal therapy. We summarize the components of organ-preserving treatment, including radiation therapy, its state-of-the-art technology, results and side effects. The results and toxicity of trimodal treatment are compared with those of radical cystectomy.

The role of brachytherapy in the curative treatment of oral cavity tumors / A brachytherapia szerepe az ajak-szájüregi daganatok kuratív ellátásában.

Összefoglaló. A szájüregi daganatok kuratív kezelésében az elsodlegesen választandó mutét mellett a sugárterápiának is jelentos szerepe van. A lokális tumormentesség biztosításához azonban dóziseszkaláció szükséges. Ennek külso besugárzással való megvalósítása a környezo normálszövetek fölösleges dózisterhelésével és az ebbol következo mellékhatások elofordulásának emelkedésével jár. A brachytherapia (BT) - amelynek során radioaktív sugárforrást/sugárforrásokat juttatunk a tumorba vagy annak közelébe - lehetové teszi a helyileg magasabb dózis leadását a környezo ép szövetek kímélésével. A BT a korai, T1-2N0 stádiumú szájüregi tumoroknál - kedvezo prognosztikai faktorok mellett - akár kizárólagosan vagy mint posztoperatíve egyedül alkalmazott terápiás modalitás jön szóba. Kedvezotlenebb prognózis esetén vagy elorehaladottabb stádiumban (T3-4 vagy N+) a mutétet és/vagy a percutan irradiációt kiegészíto eljárásként alkalmazható kedvezo sugárfizikai tulajdonságai miatt. A kis dózisteljesítményu (low-dose-rate, LDR) BT-t már évtizedek óta alkalmazzák a terápiában, de ezt kezdi kiszorítani a nagy dózisteljesítményu (high-dose-rate, HDR), illetve a pulzáló dózisteljesítményu (pulse-dose-rate, PDR) BT. A jelen áttekinto tanulmány célja irodalmi adatok alapján a BT szerepének és indikációjának ismertetése a szájüregi daganatok kuratív kezelésében, alrégiókra lebontva. Orv Hetil. 2021; 162(37): 1471-1479. Summary. Radiation therapy plays a significant role in the curative treatment of oral cavity tumors, in addition to the primary choice of surgery. However, dose escalation is required to ensure local tumor control. Its implementation with external irradiation is accompanied by an unnecessary dose exposure to the surrounding normal tissues and an increase in the incidence of consequent side effects. Brachytherapy (BT), in which a radiation source/sources is/are placed inside or close to the tumor, allows a higher dose to be delivered locally, sparing the surrounding intact tissues. In addition to favorable prognostic factors in early T1-2N0 stage oral cavity tumors, BT is considered either exclusively or as a sole postoperative therapeutic modality. At less favorable prognosis or at a more advanced stage (T3-4 or N+), BT can be used as a complementary procedure after surgery and/or percutaneous irradiation based on its favorable radio-physical properties. Low-dose-rate (LDR) BT has been used in the therapy for decades, but recently it has been replaced by high-dose-rate (HDR) and pulse-dose-rate (PDR) BT. The purpose of this review is to describe the role and indications of BT in the treatment of oral cavity tumors categorized into subregions, based on the literature data. Orv Hetil. 2021; 162(37): 1471-1479.

Clinical importance of retropharyngeal lymph node metastases / A retropharyngealis nyirokcsomóáttétek klinikai jelentosége.

Összefoglaló. A retropharyngealis nyirokcsomóáttétek incidenciája a primer fej-nyaki daganat lokalizációjától függ. Leggyakrabban az elorehaladott vagy recidív nasopharynx-carcinomák esetén fordul elo, de III-IV. stádiumú oro- és hypopharynxtumorok esetén is megjelenhetnek. Non-nasopharyngealis primer tumoroknál a manifesztációjuk kedvezotlen prognosztikai faktornak tekintheto, melynek hátterében a diagnosztikus nehézség miatti késoi detektálás, a kifejezetten nehéz sebészi eltávolíthatóság, valamint az agresszív biológiai viselkedés állhat. Az esetismertetésünkben bemutatásra kerülo, 58 éves betegünknél bal oldali elülso szájfenéki primer tumort diagnosztizáltunk azonos oldali nyaki és retropharyngealis nyirokcsomó-metastasissal, mely a nemzetközi irodalom alapján extrém raritás, incidenciája kevesebb mint 1%. A retropharyngealis nyirokcsomók diagnosztikájában a lokalizáció miatt a képalkotóknak jut hangsúlyosabb szerep. Elhelyezkedésük nemcsak diagnosztikus, hanem sebésztechnikai kihívást is jelentenek az életfontosságú anatómiai képletek közelsége, illetve a szuk feltárási viszonyok miatt. Ilyenformán ezek a mutétek csak intenzív osztályos háttérrel és kello jártassággal rendelkezo centrumokban végezhetok. Az alapvetoen rossz prognózist a korai diagnózis és a multimodális terápia kedvezoen befolyásolja. Esetünkben a komplex kezeléssel (sebészi terápia és posztoperatív radiokemoterápia) sikerült lokoregionális tumormentességet elérni, és ezzel a teljes és a betegségmentes túlélési idot növelni. Orv Hetil. 2021; 162(25): 997-1003. Summary. The incidence of retropharyngeal lymph node metastasis depends on the localization of the primary head and neck cancer. Involved nodes are seen most commonly in cases of advanced or recurrent nasopharyngeal carcinoma, however, they might occur with stage III-IV oro- and hypopharyngeal tumours. The involvement of retropharyngeal lymph nodes has been associated with poor outcome of non-nasopharyngeal primary tumours, which might be explained by the delayed diagnosis, the difficult surgical procedure in the retropharyngeal space, and the aggressive nature of the disease. Here we present the case of a 58-year-old patient with an anterior oral cavity tumour on the left side with ipsilateral cervical lymph node and retropharyngeal lymph node metastases, which has been noted an extreme rarity in the literature with less than 1% incidence. Due to the localization of the retropharyngeal lymph nodes, the detection is based on imaging modalities. It represents a challenge for diagnosis and surgical treatment due to the close proximity of vital anatomical structures. Accordingly, these operations should only be performed in specialist surgical centres with intensive care units. The early diagnosis and the multimodality treatment might have a positive effect on the poor prognosis. In our case, we managed to achieve locoregional disease-free status with the complex treatment (surgical therapy and postoperative radiochemotherapy) and increase the overall and the disease-free survival. Orv Hetil. 2021; 162(25): 997-1003.

[Mutagen sensitivity and risk of second cancer in young patients with head and neck squamous cell cancer]. / Mutagénérzékenység és második primer daganat kialakulása fiatal fej-nyaki laphámrákos betegeknél.

Head and neck cancer patients are at high risk for secondary primary cancer (SPC) development. Mutagen hypersensitivity may be associated with elevated risk of SPC. A survey was made of SPC among 124 young (≤50 years) patients with squamous cell carcinoma of the head and neck who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (>1 b/c) or not hypersensitive (≤1 b/c). The mean follow-up time was 64 months (range: 5-244 months). Eighteen patients (15%) developed a SPC. The 10-year estimated rate of SPC for hypersensitive (n=65) or not hypersensitive (n=59) patients were 17% and 30%, respectively (p=0.4272). Thirty-nine percent of SPC was developed after 10-year follow-up. The 5-year cancer-specific survival was 17% following the development of SPC. According to our findings, mutagen hypersensitivity does not increase the risk of developing SPC.

Chromosomal Aberrations in Blood Lymphocytes as Predictors of Respiratory Function After Stereotactic Lung Irradiation.

Due to the profound difference in radiosensitivity of patients and various side effects caused by this phenomenon, a radiosensitivity marker is needed. Prediction by a marker may help personalise the treatment. In this study, we tested chromosomal aberrations (CA) of in vitro irradiated blood as predictor of pulmonary function decrease of nonsmall cell lung cancer (NSCLC) patients and also compared it with the CAs in the blood of irradiated patients. Peripheral blood samples were taken from 45 lung cancer patients before stereotactic radiotherapy (SBRT) and immediately after the last fraction and 3, 6, 9, 12, 15, 18, 21, and 24 months later. Respiratory function measurements were performed at the same time. Diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1s), and FEV1s/FVC (FEV1%) were monitored. Metaphase preparations of lymphocytes were made with standard procedures, and chromosome aberrations were analysed. In our cohort, the 36-month local relapse-free survival was 97.4%, and the distant metastasis-free survival was 71.5% at 36 months. There was no change in the mean of the pulmonary function tests (PFTs) after the therapy. However, there was a considerable variability between the patients. Therefore, we subtracted the baseline and normalised the PFT values. There were significant decreases at 12-24 months in relative FEV1s and relative FEV1%. The tendentious decrease of the PFTs could be predicted by the in vitro chromosome aberration data. We also found connections between the in vitro and in vivo CA values (i.e., dicentrics plus rings after 3 Gy irradiation predicts dicentric-plus-ring value directly after the radiotherapy/V54 Gy (p = 0.001 24.2%)). We found that-after further validation-chromosome aberrations resulted from in vitro irradiation before radiotherapy can be a predictive marker of pulmonary function decrease after lung irradiation.

Results of postoperative interstitial brachytherapy of resectable floor of mouth tumors.

PURPOSE: The purpose of this study was to describe the results of postoperative sole interstitial brachytherapy (BT) in patients with resectable floor of mouth tumors. METHODS AND MATERIALS: Between January 1998 and December 2017, 44 patients with squamous cell histology, stage T1-3N0-1M0 floor of mouth tumor were treated by excision of the primary lesion with or without neck dissection followed by sole high-dose-rate tumor bed BT with an average dose of 22.7 Gy (10-45 Gy) using rigid metal needles (n = 14; 32%) or flexible plastic catheters (n = 30; 68%). RESULTS: During a median followup time of 122 months for surviving patients, the probability of 5- and 10-year local and regional tumor control, overall survival (OS), and disease-specific survival (DSS) was 89% and 89%, 73% and 67%, 52% and 32%, 66% and 54%, respectively. In univariate analysis, lymphovascular invasion was a negative predictor of regional tumor control (p = 0.0062), DSS (p = 0.0056), and OS (p = 0.0325), whereas cervical recurrence was associated with worse DSS (p < 0.0001) and OS (p < 0.0001). The incidence of local Grade 1, 2, and 3 mucositis was 25%, 64%, and 11%, respectively. Grade 4 side effect, that is soft tissue necrosis occurred in four cases (9%). CONCLUSIONS: Results of postoperative sole high-dose-rate BT of floor of mouth tumors are comparable with those reported with low-dose-rate BT, and this method could improve local tumor control and DSS compared with exclusive surgical treatment.

Breast-Conserving Surgery Followed by Partial or Whole Breast Irradiation: Twenty-Year Results of a Phase 3 Clinical Study.

PURPOSE: To report the 20-year results of a phase 3 clinical trial comparing the survival and cosmetic results of breast-conserving surgery followed by partial breast irradiation (PBI) or whole breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and 2004, 258 selected patients with low-risk invasive breast carcinoma (pT1 pN0-1mi, grade 1-2, nonlobular breast cancer) resected with negative margins were randomized after breast-conserving surgery to receive PBI (n = 128) or 50 Gy WBI (n = 130). Partial breast irradiation was given either by multicatheter high-dose-rate (HDR) brachytherapy (BT; n = 88) with 7 × 5.2 Gy twice daily or 50 Gy external beam irradiation with electron beams (n = 40). RESULTS: Median follow-up time was 17 years. The 20-year actuarial rates of ipsilateral breast tumor recurrences were 9.6% versus 7.9% (P = .59) in the PBI and WBI arms, respectively. There was no significant difference in the 20-year probability of disease-free (79.7% vs 78.3%), cancer-specific (92.6% vs 88.1%), and overall survival (59.5% vs 59.7%). Significantly more patients had excellent or good cosmetic result in the PBI and WBI groups (79.2% vs 59.5%; P = .0007). CONCLUSIONS: The 20-year updated results of our phase 3 clinical trial add further scientific evidence that PBI either with multicatheter HDR BT or electron beams for low-risk invasive breast carcinomas yield long-term local tumor control and survival comparable to those achieved with standard WBI. Interstitial HDR BT improved cosmetic results compared with WBI.