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Biomedical subjects

Barbara A Jereczek-Fossa

Publications and source records attributed to Barbara A Jereczek-Fossa.

16 recordsLinked to original sources

Endoscopic CO2 laser surgery for early glottic cancer in patients who are candidates for radiotherapy: results of a prospective nonrandomized study.

BACKGROUND: Treatment of early glottic malignancies is controversial, particularly if postoperative endoscopy shows minimal/no residual disease. METHODS: In a prospective nonrandomized study, we performed endoscopic laser surgery with curative intent in 59 patients with early glottic carcinoma presenting for radiotherapy after diagnosis elsewhere by random biopsy or cordal stripping. We analyzed outcomes and residual cancer in the specimen. RESULTS: Clinical staging elsewhere did not correspond to (usually underestimated) the pathologic stage in 60.7%. In 22%, no tumor was identified on pathologic examination. After 35.3 months (mean), 93.2% were alive with no evidence of disease. Local control was achieved in 98.3% of the patients, and 13.5% of the patients required radiotherapy. The larynx was conserved in 98.3%. CONCLUSIONS: Biopsy/stripping are best abandoned for persistent glottic lesions. A single laser endoscopic procedure provides reliable staging and definitive treatment in most cases using fewer resources. Biopsied patients presenting for treatment should be offered laser surgery as an alternative to radiotherapy.

Adult↗

Branchiogenic carcinoma--conceptual or true clinico-pathological entity?

The existence of branchiogenic carcinoma remains controversial. According to some authors, this malignancy is more conceptual than a true clinicopathologic entity. The originally proposed diagnostic criteria of branchiogenic carcinoma have been subsequently challenged. Many reports regarding primary branchiogenic carcinoma have failed to provide sufficient evidence to distinguish this entity from nodal metastases arising from unrecognized primary tumours. There is growing evidence that the majority of branchiogenic carcinomas are in fact cystic metastases from oropharyngeal carcinoma, most commonly originating in the tonsils, and not true carcinomas arising in a branchial cleft cyst. The missing link between branchial cyst and branchiogenic squamous cell carcinoma could be fulfilled by the occurrence of in situ branchial cyst carcinomas, yet such cases are extremely rare. Isolated cystic neck lesions, necessitate a thorough search for a primary tumour, similarly to other occult primaries presenting with cervical metastases. The treatment of cervical cyst with dysplasia or carcinoma in situ includes complete surgical excision. The true branchiogenic carcinomas should be approached with postoperative irradiation to the half neck. A cervical metastatic cystic squamous carcinoma of unknown origin should be treated as for other cases of occult primaries, i.e. with surgery and radiotherapy. The data on the prognosis of branchiogenic carcinoma are scarce, though long-term survival has been reported. Further histopathologic and clinical studies are warranted in order to better understand the biology and natural history of cervical cystic lesions. The existence of true branchiogenic carcinoma remains to be verified with new clinical and molecular criteria.

Biopsy↗

Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An analysis of 43 consecutive patients.

BACKGROUND: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.

Adolescent↗

Clinical and research validity of hadrontherapy with ion beams.

Clinical results obtained with hadrontherapy have been extremely positive for various tumours, with percentages of local control and survival higher than those ascribed to conventional radiotherapy. Most clinical data obtained with charged particles are related to protontherapy but the implementation of carbon ion therapy has demonstrated to be of great interest in the last decade. These results, accompanied by the new performances in accelerator technology and calculation systems of the delivered doses, have determined over the past years an increased interest for the development of hadrontherapy, with the construction of new centres provided with equipment entirely dedicated to clinical activity (LLUMC, Loma Linda and NPTC, Boston in USA, HIMAC-NIRS, Chiba, PROBEAT, Tsukuba, and Hyogo Beam Medical Centres in Japan). A revision of the clinical indications specifically focused on ion therapy is presented as well as the results obtained in the different centres. With hadrontherapy, it is finally possible to increase the spectrum of treatments allowing preserving the organ and its functionality, with positive impacts from a social and economic point of view.

Animals↗

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary.

Cervical lymph node metastases of squamous cell carcinoma from occult primary constitute about 2-5% of all patients with carcinoma of unknown primary site (CUP). Metastases in the upper and middle neck are generally attributed to head and neck cancers, whereas the lower neck (supraclavicular area) involvement is often associated with primary malignancies below the clavicles. The diagnostic procedures include physical examination with thorough evaluation of the head and neck mucosa using fiber-optic endoscopy, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computer tomography and/or magnetic resonance. A systematic tonsillectomy in the absence of suspicious lesions is often recommended since up to 25% of primary tumors can be detected in this site. The thoracic primary (tracheal, bronchial, lung, esophagus) has to be excluded, especially in the case of lower neck involvement. Positron emission tomography (PET) with fluoro-2-deoxy-D-glucose allows detection of primary tumor in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (lymph node excision or neck dissection), with or without postoperative radiotherapy, radiotherapy alone and radiotherapy followed by surgery. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) necessitate combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighted against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Carcinoma, Squamous Cell↗

Radiotherapy-induced thyroid disorders.

Despite their specific functional consequences, radiotherapy-induced thyroid abnormalities remain under-estimated and underreported. These sequelae may include primary or central hypothyroidism, thyroiditis, Graves' disease, euthyroid Graves' ophthalmopathy, benign adenomas, multinodular goitre and radiation-induced thyroid carcinoma. Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, affects 20-30% of patients administered following curative radiotherapy to the neck region, with approximately half of the events occurring within the first 5 years after therapy. The relative risk of radiation-induced cancer (mainly well-differentiated tumours) is 15-53-fold higher than in non-irradiated population. The aetiology of radiation-induced thyroid injury includes vascular damage, parenchymal cell damage and auto-immune reactions. Total radiotherapy dose, irradiated volume of the thyroid gland, and the extent of prior thyroid resection are among the most important factors associated with the risk of hypothyroidism. The contribution of other treatment modalities (chemotherapy, endocrine therapy) as well as patient- and tumour-related factors is less clear. Reduction in radiation dose to the thyroid gland and hypothalamic/pituitary complex should be attempted whenever possible. New radiotherapy techniques, such as stereotactic radiosurgery, three-dimensional conformal irradiation, intensity modulated radiotherapy and proton therapy allow generally better dose distribution with lower dose to the non-target organs. The diagnostic approach to thyroid radiation injury includes baseline thyroid function assays in all patients undergoing thyroid or parasellar irradiation. Recommended follow-up procedures include at least annual evaluation with a history for symptoms of thyroid dysfunction, clinical examination, and measurement of thyroid hormones and thyrotropin. Management of overt hypothyroidism is based on hormone replacement therapy. Thyroid hormone therapy is also recommended in cases of subclinical hypothyroidism. Treatment of other radiation-induced thyroid disorders (thyroiditis, Graves' disease, thyroid cancer) is similar to that employed in spontaneously occurring conditions. Further improvements in radiotherapy techniques and progress in endocrine diagnostics and therapy may allow better prevention and management of radiation-related thyroid injury.

Adenoma↗

Time without symptoms and toxicity (TWIST) analysis of adjuvant radiation therapy for endometrial cancer.

BACKGROUND AND PURPOSE: Postoperative radiotherapy in endometrial cancer reduces the risk of local relapse but is also associated with substantial acute and late reactions. The aim of our study was to evaluate time without tumor symptoms and toxicity (TWIST) in a consecutive series of 317 endometrial cancer patients administered postoperative irradiation. PATIENTS AND METHODS: Both low-dose rate brachytherapy (BRT) and external beam irradiation (EBRT) were applied in 247 patients (78%), only BRT--in 49 (15%) and only EBRT--in 21 patients (7%). Median follow-up was 7.3 years (range, 4-21 years). TWIST analysis based on actuarial freedom from recurrent disease and from late radiotherapy effects was performed with the use of Kaplan-Meier method. The impact of patient- and treatment-related factors on TWIST was assessed with uni- and multivariate tests. RESULTS: Five-year overall survival was 78%, and five-year disease free survival--75%. Recurrence occurred in 70 patients (22%), of whom in 11 (3.5%)--exclusively in the pelvis. Acute and late reactions of any grade occurred in 268 (85%) and 158 patients (51%), respectively. Late bowel effects of any grade were observed in 41% of patients. Severe late effects occurred in 35 patients (11%). Actuarial probability of two- and five-year survival free of disease and severe (grades 3 or 4) late effects (TWIST) was 84% and 71%, respectively (median TWIST, 16.2 years). When all-grade late effects were considered, two- and five-year TWIST probability was 50 and 30%, respectively, and median TWIST was only 2.0 years. When both acute and late reactions were taken into account, median TWIST was 22 months. In unifactorial test, higher age ( P = 0.013) FIGO stage ( P < 0.001) total radiotherapy dose ( P < 0.001) normalized total dose based on linear-quadratic model ( P = 0.001) EBRT fraction dose ( P < 0.001) and use of cesium BRT ( P = 0.042) were correlated with shorter TWIST. In multifactorial analysis, higher age ( P = 0.001) FIGO stage ( P = 0.001) and total radiotherapy dose ( P < 0.001) were independent factors correlated with shorter TWIST. CONCLUSIONS: Endometrial cancer patients treated with postoperative irradiation have a long time interval without relapse and severe late toxicity. However, when any late normal tissue injury is considered, the median time without relapse and late toxicity is significantly shorter. The impact of mild late radiotherapy complications on the quality of life should be further investigated. TWIST calculation should be attempted in future prospective studies evaluating the role of postoperative radiotherapy.

Adenocarcinoma↗

Male breast cancer: a special therapeutic problem. Anything new? (Review).

Carcinoma of the male breast (MBC) is an uncommon phenomenon, accounting for <1% of all malignancies in man. It represents a biologically heterogeneous disorder, and its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Most of our current knowledge regarding its biology, natural history, and treatment strategies has been extrapolated from its female counterpart. Information regarding prognostic relevance of new molecular markers is limited. At the European Institute of Oncology we performed a study showing data in which p21Waf1 and p27Kip1 proteins were evaluated in a series of male breast cancer patients. Our data suggest that the immunohistochemical evaluation of p21Waf1 and p27Kip1 expression in male breast carcinomas may be a further useful marker for selecting patients who express functional proteins that can be predictive for the most efficient endocrine response. Moreover, searching for more conservative treatment, we introduced in our clinical practice sentinel node biopsy, and if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information. Male breast cancer has biological differences compared with female breast cancer. It responds to hormonal manipulation and chemotherapy, but optimal treatment regimens in males are unknown. By analogy to the female breast cancer, post-mastectomy radiotherapy should be proposed in case of advanced T stage and/or lymph node positivity (considering the small volume of the male mammary gland, we suggest post-mastectomy irradiation in case of T >1 cm and/or presence of >1 metastatic axillary lymph node). Breast conserving surgery, performed in selected cases of male breast cancer, should be always followed by radiotherapy. Despite a wealth of small retrospective studies on MBC, its rarity means there is a lack of prospective randomized controlled treatment trials, which needs to be addressed if significant advances are to be made in the treatment of this unusual challenging disease.

Breast Neoplasms, Male↗

Analysis of mandibular dose distribution in radiotherapy for oropharyngeal cancer: dosimetric and clinical results in 18 patients.

BACKGROUND AND PURPOSE: The relationship between the radiation dose and the risk of the osteoradionecrosis is well known. However, the dose to the mandible is not routinely assessed in the radiotherapy for head and neck cancer. The aim of our study was to analyze the mandibular dose distribution in the patients administered curative radiotherapy for squamous cell carcinoma of the oropharynx. Moreover, the clinical results have been analyzed. MATERIAL AND METHODS: We examined the clinical records and treatment plans in 18 patients treated with bifractionated radiotherapy for stage II-IV oropharyngeal cancer. In 17 patients, the total radiotherapy dose prescribed in the International Committee of Radiation Units and Measurements (ICRU) reference point was 74.4 Gy administered in 62 fractions (1.2 Gy twice daily with 6h interfraction interval) and one patient received a dose of 75.6 Gy. The whole dose to the mandibular-orophryngeal region was delivered with 6 MV photons. The mandible was contoured manually on computed tomographic scans and the point doses at the both mandibular condyles, ascending ramus, mental symphysis, molar and retromolar regions were assessed. Moreover, the cumulative dose-volume histograms (DHVs) were evaluated. The median follow-up period for alive patients is 30 months (range, 21-44+ months). RESULTS: Tumor remission was observed in 17 patients: in 11 cases, complete remission was achieved and in six cases, only partial remission was possible. One patient was lost to follow-up before the first response evaluation. The median survival for all patients is 22 months (range, 3-44+ months). Ten patients are alive and seven died. In six cases, the cause of death was head and neck tumor and in one died due to pancreatic cancer (second primary). No late bone post-radiation complication was seen. The highest radiotherapy doses were observed in the retromolar regions. The mean percentage doses at the right and left retromolar regions were 101.3+/-3.8% (range, 90.2-109.1%) and 101.7+/-2.5% (range, 95.2-105.8%), respectively. Lower doses were seen in ascending ramus (the mean percentage doses at right and left ascending ramus were 97.3+/-8.5% and 97.8+/-7.6%, respectively), the molar regions (the mean percentage doses at right and left molar regions were 86.0+/-13.5% and 88.1+/-12.9%, respectively), and at the mandibular condyles (the mean percentage doses at the right and left mandibular condyles were 72.6+/-18% and 77.0+/-16.5%, respectively). The volume of the mandible ranged from 60.1 to 110.1cm(3) (a mean of of 82.3 cm(3)). In all patients, the maximum dose absorbed in the mandible was higher than the dose prescribed in the ICRU point and the mean maximum dose absorbed in the mandible was 105.7+/-2.1% (range, 102.4-110.6%). The percentage of mandibular volume receiving a dose higher than prescribed was 28.6+/-14.9% (range 10.2-58.1%). The area underlying the DVH curve, the maximum mandibular doses and the retromolar doses did not appear to statistically depend on use of wedge or mandibular volume. CONCLUSIONS: Radiotherapy for oropharyngeal cancer is associated with high doses to the retromolar mandibular regions (the dose can be higher than prescribed in the ICRU reference point), ascending ramus and molar regions. Lower doses are absorbed at the condyles and mental symphysis. The single dose point (for example, the ICRU reference point) could be not used as a representative for the mandibular dose. In our small series of patients treated with hyperfractionated irradiation, these dose heterogeneities were not correlated to the patient- and treatment-related factors and are not related to the increased risk of late bone complications. The clinical relevance of mandibular dose distribution remains to be established in larger series of patients treated with conventionally and unconventionally fractionated irradiation.

Adult↗

Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases.

BACKGROUND AND PURPOSE: Acute radiotherapy reactions are commonly underestimated and under-reported in the literature. Our aim was to evaluate the incidence and risk factors for acute reactions during postoperative radiotherapy in endometrial cancer patients. MATERIAL AND METHODS: Performed was detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. Two hundred forty seven patients (78%) received both intracavitary (BRT) and external beam irradiation (EBRT), 49 patients (15%) received only BRT and 21 patients (7%) - only EBRT. BRT included radium (Ra) or cesium (Cs). The mean total dose at 0.5 cm for Ra and Cs was 50.5+/-10.3 Gy and 48.4+/-15.0 Gy, respectively, and the mean dose rate - 0.47+/-0.06 Gy/h and 1.42+/-0.41 Gy/h, respectively. Mean EBRT dose in the ICRU reference point was 49.0+/-3.7 Gy given in fractions of 1.54-2.49 Gy (mean 2.0+/-0.17 Gy). Radiotherapy and Oncology Group classification system was employed to score acute reactions. The impact of patient- and treatment-related factors on the risk of acute bowel and urinary bladder reactions was assessed with uni- and multivariate tests. RESULTS: Acute radiotherapy reactions of any grade occurred in 265 patients (84%) including bowel complications in 66% and urinary bladder complications in 36%. There were 21 severe (grade 3 or 4) reactions, all but one seen in the patients treated with combined EBRT and BRT. Higher total dose (P=0.024), higher EBRT dose (P=0.022) and higher age (P=0.026) were correlated with increased acute bowel toxicity in univariate analysis. Multivariate analysis showed that higher EBRT dose (P=0.015) and older age (P=0.016) were independently correlated with the risk of acute bowel events. Higher total dose (P=0.009), BRT dose (P=0.029), BRT dose rate (P=0.004), EBRT fraction size (P=0.007), the use of Cs BRT (P=0.001) and lower parity (P=0.041) were correlated with increased risk of acute bladder toxicity in univariate test. Multivariate analysis demonstrated that the independent risk factors for acute bladder events were BRT dose rate (P=0.002) and low parity (P=0.042) and there was a trend for EBRT dose (P=0.076). In multivariate analysis there was no impact of other clinical factors (FIGO stage, diabetes mellitus, hypertension, prior abdominal surgery) on the risk of acute bowel and/or bladder reactions nor was the impact of surgery-to-radiotherapy interval, overall radiotherapy time and overall treatment time. CONCLUSIONS: The risk of acute reactions depends both on treatment-related (BRT dose rate, EBRT dose) and patient-related factors (age, parity). Precise treatment prescription, planning and verification are of paramount concern. Further studies are warranted to evaluate the impact of extrinsic and intrinsic factors associated with acute normal tissue injury.

Adult↗

Radiotherapy-induced ear toxicity.

Despite their particular functional consequences, radiotherapy-induced ear injuries remain under-evaluated and under-reported. These reactions may have acute or late character, may affect all structures of the hearing organ, and result in conductive, sensorineural or mixed hearing loss. Up to 40% of patients have acute middle ear side effects during radical irradiation including acoustic structures and about one-third of patients develop late sensorineural hearing loss (SNHL). Total radiotherapy dose and tumour site seem to be among the most important factors associated with the risk of hearing impairment. Thus, reduction in radiation dose to the auditory structures should be attempted whenever possible. New radiotherapy techniques (3-dimensional conformal irradiation, intensity modulated radiotherapy, proton therapy) allow better dose distribution with lower dose to the non-target organs. Treatment of acute and late external otitis is mainly conservative and includes the anti-inflammatory agents (applied topically and systematically). Post-radiation chronic otitis media and the eustachian tube pathology may be managed with tympanic membrane incision with insertion of a tympanostomy tube (grommet), although the benefit of such approach is controversial and some authors advocate a more conservative approach. In these patients the functional deficit can be alleviated by application of bone conduction hearing aids such as, e.g., the bone anchored hearing aid (BAHA). There is no standard therapy for post-irradiation sudden or progressive SNHL yet corticosteroid therapy, rheologic medications, hyperbaric oxygen or carbogen therapy are usually employed (as for idiopathic SNHL), although controversial data on the efficacy of these treatment modalities have been published. In selected cases with bilateral profound hearing loss or total deafness, cochlear implants may prove effective. Further improvements in radiotherapy techniques and progress in otologic diagnostics and therapy may allow better prevention and management of radiation-related acoustic injury.

Audiometry↗

Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer.

PURPOSE: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). METHODS: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. RESULTS: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p = 0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p <0.001 and p = 0.47, respectively). The severity of acute bowel and bladder toxicity did not correlate with the time to occurrence of late toxicity in these locations (p = 0.34 and p = 0.47, respectively). CONCLUSION: Patients with increased acute bowel toxicity during postoperative RT for endometrial cancer have an increased risk of late bowel injury. A higher grade of acute bowel complications correlated with more severe late events, but was not predictive for its latency time. These findings suggest the possibility of an early indication of patients with an increased risk of late toxicity in whom preventive measures might be attempted.

Adult↗

Radiotherapy-induced mandibular bone complications.

The mandible is among the bones most frequently affected by irradiation. The most severe post-radiation injury of the mandible is osteoradionecrosis (ORN). Conflicting data have been reported on the incidence of this complication, its aetiology and management. The incidence of mandibular ORN in head and neck cancer patients managed with radical or postoperative irradiation, has varied widely in the literature from 0.4% to 56%. The interpretation of data derived from particular series are difficult due to the different scoring methods and classification systems used for the evaluation of post-radiation bone damage. Although ORN occurs typically in the first three years after radiotherapy, patients probably remain at indefinite risk. The diagnosis of ORN is principally based on the clinical picture of chronically exposed bone. Radiological symptoms include decreased bone density with fractures, cortical destruction and loss of spongiosa trabeculation. Numerous factors that may be associated with the risk of ORN include treatment-related variables (for example, total radiotherapy dose, biologically effective dose, photon energy, brachytherapy dose rate, combination of external beam irradiation and interstitial brachytherapy, field size, fraction size, volume of the mandible irradiated with a high dose), patient-related variables (like deep parodontitis, pre-irradiation bone surgery, bad oral hygiene, alcohol and tobacco abuse, bone inflammation, dental extraction after radiotherapy) and tumour-related factors (tumour size or stage, proximity of the tumour to bone, anatomic tumour site). Primary management of post-radiation bone lesions include conservative modalities such as saline irrigations, antibiotics during infectious episodes, topically applied antiseptics, gentle sequestrectomy and removal of visibly loosened bone elements as well as treatment with hyperbaric oxygen (HBO). Surgery is reserved for persistent ORN and includes radical resection of the lesion(sequestrectomy, hemimandibulectomy etc.) with reconstruction. In recent years the introduction of preventive oral hygiene measures and meticulous dental evaluations before and after irradiation, improvement in radiotherapy techniques and the development of reliable diagnostic and therapeutic procedures have resulted in a decreased incidence of ORN. Nevertheless, given the severe impact of ORN on patient quality of life, research should be continued to further ameliorate this problem.

Head and Neck Neoplasms↗

Phase II trial of vinorelbine, cisplatin and continuous infusion of 5-fluorouracil followed by hyperfractionated radiotherapy in locally advanced head and neck cancer.

OBJECTIVE: We undertook a prospective phase II study to assess the feasibility and activity of a new induction chemotherapy regimen followed by hyperfractionated irradiation in locally advanced squamous cell head and neck cancer. METHODS: 25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m(2) i.v. day 1) and 5-fluorouracil (200 mg/m(2) continuous i.v. infusion day 1-21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily. RESULTS: Chemotherapy was well tolerated, 6 patients developed grade 3 and one patient grade 4 neutropenia. Response to chemotherapy was observed in 19 patients (76%) including three complete responses and 16 partial responses. Planned bidRT was completed in 25 patients and all but one received planned bidRT dose without interruptions. Radiotherapy was well tolerated, mucositis was the most common side effect (grade 3-12 patients, grade 4-1 patient). At evaluation after the completion of bidRT, 13 patients had complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor progression. At the median follow-up of 18.2 months, 11 patients were alive and free of disease, and 14 patients had died (12 of tumor). Late xerostomy was observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1 patient. CONCLUSIONS: bidRT preceded by ViFuP seems a feasible and active combination in locally advanced head and neck cancer. Good patient compliance did not compromise the delivery of planned dose of bidRT. However, short median duration of response (14.6 months) and moderate median overall survival (18.7 months) indicate the need for more intensive therapeutic strategies. On the basis of these results, modifications of our treatment schedule (shortening the overall treatment time by reduction of chemotherapy cycles and the use of chemotherapy concomitantly with irradiation) are planned for the future study.

Adolescent↗

Guidelines for the delineation of nodal regions of the head and neck on axial computed tomography images.

Delineation of target volumes is increasingly recognized as the most crucial step within the process of modern conformal radiotherapy. In the field of head and neck radiation oncology, the need for a standardized methodology in the delineation of nodal regions of the neck on computed tomography (CT) images has recently emerged. To address this issue, a consensus document has been prepared by the Head and Neck Working Party of the AIRO-Lombardia Cooperative Group, based on the proceedings of multidisciplinary meetings and on literature findings. The document contains detailed guidelines for the delineation on CT images of the nodal regions of the neck, including for each nodal region (1 to 7) the description of anatomical limits as seen on CT images.

Head and Neck Neoplasms↗