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.

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.

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.

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.

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.

[Changing trends in the management of the human papillomavirus induced oropharyngeal cancer]. / Változó tendenciák a humán papillómavírus okozta szájgaratdaganatok kezelésében.

The incidence of oropharyngeal cancers caused by human papillomavirus rises sharply. They are characterized by very good therapeutic response, including radiosensitivity, as is demonstrated by the results of several retrospective analyses. In the following review publications related to this topic are introduced, (radio)biological causes of radiosensitivity are explored and the role of surgical, chemo- and biological therapeutic methods of these types of tumors are discussed with the aim to better understand their different behavior. Taking into account the younger age and better general condition of patients as well as the tumor radiosensitivity it is recommended to override the current therapeutic guidelines in respect of the doses and treatment methods primarily in order to reduce therapeutic complications. Currently several randomized trials on this subject are in progress.

[Application of CyberKnife stereotactic radiosurgery in the treatment of head and neck cancer]. / A CyberKnife sztereotaxiás sugárterápia alkalmazásának lehetõsége fej-nyaki daganatok kezelésében.

The treatment of squamous cell carcinoma of the head and neck is multimodal, including surgery, chemotherapy, and radiotherapy, or the combination of those. Though aggressive treatment results in complete tumor remission in many patients even in locally advanced stages, unfortunately local relapse is not uncommon. For patients not candidate for salvage surgery, chemotherapy and conventional fractionated external beam irradiation can be applied. However, for patients previously treated with full-dose radiotherapy, the deliverable reirradiation dose is limited, considering the elevated risk of toxicity caused by cumulative doses. CyberKnife is a highly conformal radiosurgical technology which can successfully treat this subset of patients. In addition, it can be applied for hardly resectable rare tumors of the skull base and the head and neck region like chordoma, chondrosarcoma and paragangliomas. The CyberKnife stereotacic radiosurgery technology is now available in Hungary, in the National Institute of Oncology.

[Role of MRI and CT in the evaluation of postirradiation status and complications in head and neck cancer]. / Az MRI és a CT szerepe a sugárterápia utáni státusz értékelésében, szövõdményeinek vizsgálatában, fej-nyaki daganatoknál.

Most head and neck cancer patients are treated with combined modalities such as surgery, radiotherapy (RT), chemotherapy (ChT). Concurrent chemo-radiation has improved treatment outcomes with increased toxic effects. Reactions after RT are divided into early and late changes. Early reactions are seen during the course of therapy or within 3 months; these are reversible in most cases. Late complications are observed 3 months to years after RT and they are generally irreversible. As typical late reaction radiation induced necrosis may occur in soft tissues, cartilage, bones and brain. Tumor recurrence and post-radiation necrosis typically appear at the same time, within 2-3 years after RT; the differentiation may be difficult. Computed tomography (CT) and magnetic resonance imaging (MRI) have become the gold standards not only for staging and assessing tumor response, but also to evaluate posttreatment status, to distinguish residual or recurrent tumor and RT complications. Using baseline CT or MRI between 2-3 months after treatment and performing standard follow-up imaging with strict clinical follow-up are required to establish early salvage treatment.

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer : A single institution, prospective study.

PURPOSE: To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT) METHODS AND MATERIALS: Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1-10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT. RESULTS: Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0-9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question. CONCLUSION: Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

Implementation of image-guided intensity-modulated accelerated partial breast irradiation : Three-year results of a phase II clinical study.

PURPOSE: To report 3­year results of accelerated partial breast irradiation (APBI) using image-guided intensity-modulated radiotherapy (IG-IMRT) following breast conserving surgery (BCS) for low-risk early invasive breast cancer. PATIENTS AND METHODS: Between July 2011 and March 2014, 60 patients with low-risk early invasive breast cancer underwent BCS and were enrolled in this phase II prospective study. The total dose was 36.9 Gy (9 fractions of 4.1 Gy, two fractions/day). Patient setup errors were detected in LAT, LONG and VERT directions. Local tumour control, survival results, early and late side effects and cosmetic outcome were assessed. RESULTS: At a median follow-up of 39 months, all patients were alive and neither locoregional nor distant failure occurred. One contralateral breast cancer and two new primary malignancies outside the breast were observed. No grade (G) 3-4 acute toxicity was detected. G1 and G2 erythema occurred in 21 (35%) and 2 (3.3%) patients, respectively; while G1 oedema was observed in 23 (38.8%) cases. G1 and G2 pain was reported by 6 (10%) and 2 (3.3%) patients, respectively. Among the late radiation side effects, G1 pigmentation or telangiectasia, G1 fibrosis and G1 asymptomatic fat necrosis occurred in 10 (16.7%), 7 (11.7%) and 3 (5%) patients, respectively. No ≥ G2 late toxicity was detected. Cosmetic outcome was excellent in 43 (71.7%) and good in 17 (28.3%) patients. CONCLUSION: IG-IMRT is a reproducible and feasible technique for delivery of external beam APBI following BCS for treatment of low-risk, early-stage invasive breast carcinoma. In order to avoid toxicity, image guidance performed before each radiation fraction is necessary to minimize the PTV. Three-year results are promising, early and late radiation side-effects are minimal, and cosmetic results are excellent to good.

Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer: Results of a randomized phase II study.

PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. PATIENTS AND METHODS: Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. RESULTS: Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63% following ICT + CRT, whereas 70% after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57%), LRTC (42 vs. 50%), OS (43 vs. 55%), and PFS (41 vs. 50%) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12%; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42% in the ICT + CRT and CRT groups, respectively. CONCLUSION: The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of adequate patient selection if ICT is considered.

[Dosimetry analysis of intensity-modulated and conformal radiation therapy for head and neck tumors]. / Intenzitásmodulált és konformális besugárzási tervek dozimetriai elemzése fej-nyak tumorok külsõ besugárzásánál.

The aim of the study was to compare different treatment plans - intensity-modulated and conformal - for head and neck cancer patients. Treatment plans were developed for ten head and neck cancer patients by applying four different techniques: two conventional 3D conformal plans (forward treatment planning, with two opposing fields 90o-270o and one asymmetric anterior field, matching in isocenter /Conv/, conformal parotis sparing plans /ConPas/), 3D conformal plans with inverse treatment planning techniques /INVCRT/ and intensity-modulated radiation therapy plans /IMRT/. The plans were made for the same target volumes PTV50 (elective) and PTV66 (boost-16 Gy). The cumulative dose was 66 Gy, and the Philips Pinnacle3 v8.0m TPS was used for treatment planning. The organs at risk (OAR) were as follows: spinal cord, brain stem, left and right parotis and oral cavity. The dose constrains and conditions for optimization were determined for IMRT techniques with 7 fields. During the optimization we applied two different protocols: in one case the plans were made by 40 segments for "step and shoot" IMRT techniques and by 14 segments for INVCRT, which were converted into static fields. The homogeneity (HI) and conformity (COIN) indices were calculated for planning target volumes and the comparisons were assessed on several dosimetric parameters for OARs. The IMRT, INVCRT, Conv and ConPas techniques for PTV50 planning target volume gave the following values for homogeneity index: 0.13, 0.18, 0.22, 0.19, and for conformity index: 0.76, 0.68, 0.13, 0.09. The spinal cord received a maximum of 38 Gy, 42 Gy, 45 Gy and 44 Gy for the PTV66. Mean doses of the oral cavity outside the target volume were 33 Gy, 36 Gy, 30 Gy and 48 Gy. When the 16 Gy boost treatment was applied on one side only, the mean dose for the parotis on the contralateral side was 28 Gy, 31 Gy, 49 Gy and 43 Gy, while 39 Gy, 41 Gy, 59 Gy and 53 Gy on the same side. The objectives of adequate target coverage and sparing of critical structures were fulfilled only with IMRT technique. Although the sparing of the oral cavity was the most effectively provided by the traditional technique - due to the arrangement of the fields - it gave the worst results regarding the parotis and the target volume. The highest dose for the oral cavity was given by the ConPas technique, which can cause serious early and late side effects. By increasing the number of segments for IMRT at a reasonable level, the dose for OARs can be reduced.

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.

[Our experience with targeted therapy in glioblastoma multiforme]. / Glioblastoma multiforméban szenvedo betegek célzott terápiás kezelésével szerzett tapasztalataink.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The current standard therapy includes surgical resection or biopsy, followed by a combination of radiation and chemotherapy with temozolomide. After progression or recurrence there is only one recommended effective therapy, bevacizumab. Bevacizumab is a monoclonal VEGF inhibitor antibody, inhibiting the angiogenesis in highly vascularized tumors. Resent studies focused on adjuvant treatment with targeted therapy in newly diagnosed tumors. Our purpose is to evaluate the data from patients treated in our department investigate the clinical response and side effects profile and to compare these data with the international results. The applied protocol was well tolerated and side effects corresponded to the already reported ones. The median PFS and survival data correlate with those in the literature. The AVAglio study demonstrated that the addition of bevacizumab to the adjuvant therapy increased PFS significantly.

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.

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.

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.

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.

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.