Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results.

PURPOSE: To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC. METHODS: A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c). RESULTS: Mean follow-up time for all patients was 68 months (range: 5-288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3­year cancer-specific survival was 23% with SPC. CONCLUSION: According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.

Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial.

BACKGROUND: Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated. METHODS: Eligible patients (9 with locally advanced tumour and 12 with metastases) had positive tumour EGFR expression. The cetuximab loading dose (400 mg m⁻²) was followed by 250 mg m⁻² per week. Locally advanced tumours were irradiated (mean dose 65 Gy) and treated with concomitant cisplatin (75 mg m⁻², intravenously). Patients with metastases received concomitant cisplatin and 5-fluorouracil (4 × 1000 mg m⁻²). RESULTS: For patients with locally advanced disease (median follow-up: 52 months), the median progression-free survival (PFS) was 64 months and the 2-year overall survival (OS) rate was 100%. For patients with metastases (median follow-up: 72 months), the median PFS and OS were 13 and 24 months, respectively. In both groups the objective response rate was >40%. Skin rash, in-field dermatitis, mucositis and vomiting were the most frequent grade 3/4 adverse events. CONCLUSION: In this single-arm study, the efficacy of cetuximab plus chemoradio- or chemotherapy appeared favourable as compared with historical controls. All side effects were manageable and did not hamper the treatment.

Buccal mucosal transposition flap for reconstruction of oropharyngeal-oral cavity defects: an analysis of six cases.

BACKGROUND: Operation on tumors situated in the posterior part of the oral cavity is a challenging aspect of head and neck surgery. Both the approach and the postablative reconstruction of the remaining defect require special procedures. An arsenal of reconstructive methods are available depending on the size and complexity of the defect. The goal should be to employ the simplest surgical reconstructive method, resulting in the best functional result and allowing for later complex oncotherapy. OBJECTIVE: To study the outcomes of patients treated using buccal mucosal transposition flaps for reconstruction of posterior oral cavity and oropharyngeal border defects. STUDY DESIGN: A total of 6 patients with defects of the posterior oral cavity and mesopharynx were treated with buccal mucosal transposition flaps. The patients were followed for up to 24 months. RESULTS: Defects ranging from 12 to 27 cm 2 were reconstructed with the buccal mucosal transposition flap. One patient developed an orocutaneous fistula and 1 had some trismus requiring a Z-plasty scar reorientation. One patient suffered from nasal regurgitation. Five of the 6 patients lived past 24 months, the time of follow-up of this study. CONCLUSIONS: The buccal mucosal transposition flap, with its random pattern of circulation, used alone proved to be a safe method to reconstruct soft tissue defects or line exposed hard tissues located in the posterior oral cavity and oropharynx.

Postoperative radiotherapy of childhood medulloblastomas.

The purpose of this work is to review the result of radiotherapy in the treatment of medulloblastoma in pediatric patients. Between 1986 and 1998, 66 children (45 boys and 21 girls) received postoperative irradiation in our institute. Their mean age was 8.29 years. Irradiation was performed by linear accelerator, 36 Gy were applied in the high risk group (partial tumor resection, tumor cell positivity in the liquor, metastases within the central nervous system) and 30 Gy in the low risk group (total tumor resection, negative liquor cytology, no metastases within the central nervous system) on the entire cerebrum and spinal cord. This was followed in both groups by the application of 20-20 Gy boost irradiation on the posterior scala. Studying the survival it has been found that the surgical radicality did not significantly influence the survival chances of patients, however, with the increase in the tumor size the survival chance significantly decreases (p = 0.03). When predicting life expectancy, however, the stage of tumor, the age of patients, the risk group and the M stage yielded essential information. At the age of 8 years and less, the rate of survivors is 67.6%, for those over 8 years is 75.9% (p = 0.21), however the younger age was not significant. The appearance of metastases considerably deteriorates the chances of survival (from 81.5% to 66.7%, p = 0.02). In the low risk group of patients the 5-year survival is 80%, while in the high risk group it is significantly lower, 67.4% (p = 0.04).

The importance of interstitial radiotherapy in the treatment of the base of tongue tumors: a retrospective analysis.

The authors have reviewed their experience with interstitial brachytherapy for the base of tongue cancer with the purpose of introducing treatment strategy and technique and presenting results. Between January 1993 and May 1999 twenty-one patients with primary squamous cell cancer of the base of tongue (T1-4N0-2) were treated by interstitial radiotherapy (RT). Seventeen patients with advanced stage cancer received brachytherapy (BT) boost after 60-66 Gy teletherapy and 4 patients with early stage (T1-2N0) were managed by sole BT after tumor excision and elective neck node dissection in case of positive or very narrow (< 5 mm) margin. High-dose rate (HDR) after-loading unit (Ir-192 source) was used with rigid needles or flexible plastic tubes. The treatment plan was performed by PLATO 3D BT planning system. The mean dose of boost BT or sole BT was 20 Gy (12-24 Gy) and 27 Gy (24-30 Gy), respectively. All treatments were delivered on consecutive days with a twice daily fractionation schedule, except the rigid needle technique (n = 4), where the dose was 12 Gy with a single fraction. After definitive RT of advanced stage disease, the rate of complete or partial remission was 65% (11/17) and 35% (6/17), respectively. At a mean follow-up time of 32 months the local tumor control for the entire patient population was 62% (13/ 21). Five patients (24%) died of local and/or regional failure and sixteen patients (76%) are alive (6 with local and/or regional disease and 10 without evidence of disease). All of the four sole BT treated patients belong to the latter group. The incidence of grade 2 or grade 3 mucositis was 48% and 52%, respectively. To achieve good local control with adequate doses, avoiding surgical morbidity and associated functional loss and to minimize late radiation sequelae, the combination of percutan and interstitial RT seems to be very advantageous in the treatment of the advanced tumor of the base of tongue. For patients with early stage (T1-2N0) cancer, sole postoperative BT of the tumor bed - by positive or very narrow margins - seems to be a feasible option. However, more patients and longer follow-up is required to define the value of sole BT.

[The effect of tumour bed boost on local control after breast conserving surgery. First results of the randomized boost trial of the National Institute of Oncology] / A tumorágy kiegészítô besugárzásának hatása a lokális daganatmentességre emlômegtartó mûtét után. First results of the randomized boost trial of the National Institute of Oncology.

PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC) after breast conserving surgery in a prospective study. METHODS: Between 1995 and 1998, 207 women with early invasive breast cancer who underwent conservative operation were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either no further radiotherapy (n=103) or a boost to the tumour bed (n=104) with either 16 Gy electron (n=52) or 12-14.25 Gy high dose rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude rate of local recurrence was 6.7% with and 13.6% without boost. The respective rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC, relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1% (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111), respectively, in favour of the boost group. Systemic treatments had no significant impact on LTC (88.9% with and 89.6% without systemic treatment, p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free survival was improved significantly with boost. However, the influence of boost treatment on breast cancer-specific survival should be tested in further studies. In spite of the higher incidence of late radiation side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. The final results of the EORTC trial and other ongoing studies will help to clarify the indication of boost dose according to prognostic subgroups.

[Buccal flap reconstruction of oropharyngeal defects] / Buccalis lebeny alkalmazása oropharyngealis szövetpótlásra.

AIM: Introduction of a safe and reliable method for reconstruction of soft tissue defects after excision of T1-T2 and borderline carcinomas of the posterior part of the oral cavity and mesopharynx. METHOD: Operation of two male patients suffering from tonsillolingual carcinoma, one with recurrent tumour after irradiation, the other with untreated primary and neck metastasis. After excision of the tumour with mandibular splitting method only a random buccal transposition flap was applied for reconstruction. The flap was adapted anatomically into the defect. It is a modification of previously described methods. RESULTS: Both patients healed primarily with undisturbed blood circulation of the flap. The functional rehabilitation period was short, the flap tolerated the postoperative irradiation, a moderate trismus remained after completion of the treatment, but it was not attributable to the flap. CONCLUSION: The use of the single buccal transposition flap for reconstruction of smaller defects of the posterior part of the oral cavity seems to be a simple, reliable and safe method even after irradiation. The key of the acceptable functional results is the correct adaptation of the flap

[Importance of 3D conformal percutan and brachytherapy treatment planning based on CT and MRI examinations in treatment of oral cavity tumors] / A CT- és MRT-vizsgálatokon alapuló háromdimenziós besugárzás jelentôsége szájüregi daganatoknál.

AIM: The importance of 3D conformal percutan and brachytherapy treatment planning based on CT and MRI examinations in treatment of oral cavity tumors. Introducing of the planning procedure and the selection aspects. METHOD: We present the treatment planning based on CT and MRI slices of an oral cavity tumor. The percutan or interstitial boost follow the percutan irradiation of the involved regions and lymph nodes, regarding to the target volume and the critical organs. RESULT: Our ADAC 3D planning system gives us the possibility to add the first line and the boost treatment plans, to determine and compare the dose distribution within the planned target volume and the radiation load of the critical organs. CONCLUSION: The comparative 3D radiation planning system allows higher local dose escalation required for the effective radiation treatment of oral cavity tumors with maximal protection of the surrounding healthy tissues.

[Modern radiotherapy techniques in the treatment of tumour of the base of tongue] / Nyelvgyöktumor korszerû sugárkezelése.

AIM: To demonstrate the role, the execution and the importance of the computed tomography (CT) based three-dimensional brachytherapy and conformal percutan radiotherapy in the treatment of the advanced tumour of the base of tongue. METHODS: Between January 1993 and June 2000, 27 patients with stage III-IV squamous cell cancers of the base of tongue were treated after 60 Gy percutan irradiation with interstitial, high dose rate brachytherapy (23 patients) or conformal, multi-fields radiotherapy (4 patients) as a boost. The dose of the boost irradiation varied between 12 and 24 Gy. RESULTS: Boost irradiation was well tolerated by the patients. The local tumour control at the mean follow-up period (39 months) was 52%. Using this two treatment methods in case of percutan conformal irradiation 6%, in case of brachytherapy 1.5% of the mandible received the prescribed boost dose. The spinal cord received a maximum of 15%, and 8% of the boost dose, respectively, depending on the two treatment types. CONCLUSION: With the help of these two radiotherapeutic modalities locally higher cumulative dose and better tumour control can be achieved without the higher risk of radiation injury of the surrounding normal tissues and the two most critical organs (medulla, mandible).

CT-image-based conformal brachytherapy of breast cancer. The significance of semi-3-D and 3-D treatment planning.

PURPOSE: To compare the conventional 2-D, the simulator-guided semi-3-D and the recently developed CT-guided 3-D brachytherapy treatment planning in the interstitial radiotherapy of breast cancer. PATIENTS AND METHODS: In 103 patients with T1-2, N0-1 breast cancer the tumor bed was clipped during breast conserving surgery. Fifty-two of them received boost brachytherapy after 46 to 50 Gy teletherapy and 51 patients were treated with brachytherapy alone via flexible implant tubes. Single, double and triple plane implant was used in 6, 89 and 8 cases, respectively. The dose of boost brachytherapy and sole brachytherapy prescribed to dose reference points was 3 times 4.75 Gy and 7 times 5.2 Gy, respectively. The positions of dose reference points varied according to the level (2-D, semi-3-D and 3-D) of treatment planning performed. The treatment planning was based on the 3-D reconstruction of the surgical clips, implant tubes and skin points. In all cases the implantations were planned with a semi-3-D technique aided by simulator. In 10 cases a recently developed CT-guided 3-D planning system was used. The semi-3-D and 3-D treatment plans were compared to hypothetical 2-D plans using dose-volume histograms and dose non-uniformity ratios. The values of mean central dose, mean skin dose, minimal clip dose, proportion of underdosaged clips and mean target surface dose were evaluated. The accuracy of tumor bed localization and the conformity of planning target volume and treated volume were also analyzed in each technique. RESULTS: With the help of conformal semi-3-D and 3-D brachytherapy planning we could define reference dose points, active source positions and dwell times individually. This technique decreased the mean skin dose with 22.2% and reduced the possibility of geographical miss. We could achieve the best conformity between the planning target volume and the treated volume with the CT-image based 3-D treatment planning, at the cost of worse dose homogeneity. The mean treated volume was reduced by 25.1% with semi-3-D planning, however, it was increased by 16.2% with 3-D planning, compared to the 2-D planning. CONCLUSION: The application of clips into the tumor bed and the conformal (semi-3-D and 3-D) planning help to avoid geographical miss. CT is suitable for 3-D brachytherapy planning. Better local control with less side effects might be achieved with these new techniques. Conformal 3-D brachytherapy calls for new treatment planning concepts, taking the irregular 3-D shape of the target volume into account. The routine clinical application of image-based 3-D brachytherapy is a real aim in the very close future.

Possibilities of preventing osteoradionecrosis during complex therapy of tumors of the oral cavity.

In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or postoperative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.

Sole brachytherapy of the tumor bed after breast conserving surgery: a new radiotherapeutic strategy for patients at low risk of local relapse.

The aim of the study was to test the hypothesis, if there were subgroups of early breast cancer patients in which sole brachytherapy (BT) of the tumor bed was a feasible and safe treatment option after breast conserving surgery (BCS). Forty four prospectively selected patients with Stage I-II breast cancer were entered into a protocol of postoperative tumor bed irradiation using interstitial high dose rate (HDR) implants. The HDR fractionation schedules were calculated according to the linear quadratic model. In 8 patients 7 x 4.33 Gy, in the other 36 patients 7 x 5.2 Gy were delivered to the tumor bed with 2 cm margin. The treatment planning was based on the 3 dimensional (3D) reconstruction of the clipped excision cavity, catheters and skin points. A conformal semi-3D dose planning was used. The side effects were assessed by mammograms, MRI- and clinical examinations. At a median follow up of 20 (7-36) months 1 (2.3%) local and 1 (2.3%) regional failure was observed. Distant metastasis did not occur. The cosmetic results were judged to be excellent in each case. G2 radiation side effects were observed in 2 (4.5%) cases. Postoperative sole BT of the tumor bed with careful patient selection and adequate quality assurance seems to be a feasible alternative to whole breast radiotherapy after BCS. Sole BT shortens the time of radiotherapy from 5-6 weeks to 5 days, and reduces the costs of treatment. The skin and volume sparing effect of interstitial irradiation may decrease the side effects of radiotherapy. A randomized study is in progress to define which subgroups of patients should be candidates for BT alone after BCS.