Hypothyroidism after radiotherapy for laryngeal cancer.

PURPOSE: To investigate the incidence of hypothyroidism after radiotherapy of laryngeal cancer, including the possible factors that could predict the onset of hypothyroidism. MATERIALS AND METHODS: We report this study on patients treated by radiotherapy as part of the treatment for laryngeal cancer in the Department of Oncology in Eastern Finland. Sixty-five males and seven females were treated with radiotherapy between 1974-1995.Thyroid function was determined by measuring serum thyroid stimulating hormone, and serum free thyroxine (FT4). The studied risk factors for hypothyroidism included age, treatment modalities, radiation dose and energy, height of the radiation field, and follow-up time. RESULTS: Hypothyroidism was detected in 17 (24%) of the 72 patients. Hypothyroidism was clinically unsuspected in all but one patient. Hypothyroidism was more common, if the height of the radiation field was >/=7 cm, or the patient had been operated. Hypothyroidism was less common if less than a half of the thyroid bed was irradiated. CONCLUSION: The detection of hypothyroidism clinically is difficult, and the rate of hypothyroidism warrants routine assessment of thyroid function after irradiation of laryngeal cancer.     

晚期胰腺癌术中放疗和外照射：附15例分析

本文收集1981年～1988年治疗的晚期胰腺癌15例,采用术中放疗和外照射进行治疗4例,单纯术后外照射11例.全组病例均有程度不同的姑息效果.11例生存6个～10个月,1例生存超过1.5年.本文认为,改善胰腺癌放射治疗效果,提高病变照射剂量是关键.因此开展术中放疗,术后配合外照射是行之有效的途径.     

鼻咽癌调强放疗对甲状腺血流动力学改变及功能影响的研究

背景与目的：鼻咽癌患者放射过程中,照射野包含部分或全部甲状腺,易造成甲状腺功能损伤。该研究旨在探讨调强放疗对鼻咽癌患者甲状腺血流动力学及功能变化。方法：收集2012年07月—2013年10月接受根治性放化疗初治鼻咽癌患者68例,按UICC 2010年分期为Ⅱ~Ⅳc期。采用2个周期TPF(多西他赛+顺铂+氟尿嘧啶)诱导+2个周期顺铂同期放化疗+2个周期TPF辅助治疗模式。放疗采用调强适型放疗(intensity- modulated radiation therapy,IMRT)技术。在放疗前、放疗结束即刻及结束后3和6个月通过电化学发光法检测血清中血清游离三碘甲腺原氨酸(free triiodothyronine,FT3)、血清游离甲状腺素(free thyroxin, FT4)和促甲状腺激素(thyroid-stimulating hormone,TSH)的浓度;采用甲状腺B超测量收缩期流速、舒张期流速、阻力指数、甲状腺各径线值。结果：68例鼻咽癌患者随访均满6个月。甲状腺功能减退情况：放疗结束即刻甲状腺功能减退发生率为5.9%,放疗结束后3个月甲状腺功能减退发生率为13.2%,放疗结束后6个月甲状腺功能减退发生率为26.5%。放疗结束即刻甲状腺体积变化较放疗前比较差异无统计学意义(P>0.05);在放疗结束后3、6个月甲状腺体积较放疗前比较差异有统计学意义(P<0.05)。放疗结束即刻FT3、FT4和TSH较放疗前比较差异无统计学意义(P>0.05);在放疗结束后3个月FT3、FT4、TSH较放疗前比较差异有统计学意义(P<0.05)。单因素相关分析结果显示,放疗结束即刻、结束后3、6个月甲状腺体积与甲状腺平均照射剂量均有相关性(P<0.05)。单因素相关分析结果显示,放疗结束即刻甲状腺功能减退发生率与甲状腺剂量-体积参数V40有相关性(P<0.05);独立t检验结果显示,放疗结束后6个月发现临床甲状腺功能减退病例与放疗时甲状腺接受的平均照射剂量有相关性(P<0.05)。单因素相关分析结果显示,在放疗结束即刻及结束后3、6个月甲状腺功能减退与甲状腺动脉收缩期最高流速及阻力指数无相关性(P>0.05)。结论：随着放疗结束后时间的延长,甲状腺功能减退发生率可能升高。甲状腺受照射剂量的增大、随访时间的延长,甲状腺体积可能缩小。鼻咽癌放疗后应常规复查。甲状腺剂量-体积参数V40可能是急性放射性甲状腺损伤的预测因素。该研究目前暂未发现甲状腺功能减退与甲状腺B超血流速度相关。     

局部复发鼻咽癌超分割加立体定向适形放疗的临床研究

目的:初步评价超分割外照射加立体定 向适形放射剂量治疗局部复发鼻咽癌的临床疗 效及毒副反应。方法:对1999～2002年收治的 14例复发鼻咽癌进行超分割外照射(1.3Gy/次, 2次/d,总剂量42～60Gy)加立体定向适形放射 推量(4Gy/次,隔日照射,共10次,总量20Gy) 的临床研究。结果:总有效率(CR+PR)85.7% (12/14),其中完全消退(CR)64.3%(9/14),部分 消退(PR)21.4%,肿瘤稳定14.3%,2年总生存 率57.1%(8/14),无瘤生存率42.8%(6/14),靶 区肿瘤控制率为78.6%(11/14)。结论:超分割 外照射加立体定向适形放射剂量治疗局部复发 鼻咽癌在临床上是可行及有效的。     

Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy

PURPOSE: To determine if low-dose craniospinal irradiation (2340 cGy) with chemotherapy is associated with a lower incidence of hypothyroidism compared to standard dose (3600 cGy) with or without chemotherapy in children with medulloblastoma. PATIENTS AND METHODS: Between 1980 and 1999, 32 patients < or =20 years old survived after craniospinal irradiation with or without chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI), whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a total dose 5040-5580 cGy. The median ages at the time of CSI for those receiving 2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT) was employed in 22 children. All children who received 2340 cGy had CT consisting of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%) patients receiving 3600 cGy had CT; the most common regimen was vincristine, CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone concentrations were measured in all children at variable times after radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin-releasing hormone were assessed in those suspected of having central hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years (range: 2-11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5 years (range: 2.4-20 years). RESULTS: Eighteen patients (56%) developed hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months to 18 years). Primary hypothyroidism was more common than central hypothyroidism (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15 (60%) ages 5-10 and 2 of 10 (20%) age >10 years had hypothyroidism (p < 0.001). Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10 (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT (p < 0.025). CONCLUSIONS: Current treatment regimens consisting of chemotherapy and 2340 cGy craniospinal irradiation followed by a posterior fossa boost for medulloblastoma do not show a reduction of hypothyroidism. Young age and use of chemotherapy were associated with a higher incidence of hypothyroidism.     

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability.

A potential usefulness of micronucleus assay for prediction of tumour radiosensitivity has been tested in 64 patients with advanced stage (II B-IV B) cervical carcinoma treated by radiotherapy. The study of cellular radiosensitivity in vitro was conducted in parallel with the study of cellular damage after tumour irradiation in vivo. Radiosensitivity of in vitro cultured primary cells isolated from tumour biopsies taken before radiotherapy was evaluated using cytokinesis-block micronucleus assay. Frequency of micronuclei per binucleated cell (MN/BNC) at 2 Gy was used as a measure of radiosensitivity. Radiation sensitivity in vivo was expressed as per cent increment of micronucleus frequency in cells isolated from biopsy taken after 20 Gy (external irradiation, 10 x 2 Gy) over the pre-treatment spontaneous micronucleus level and was called MN20. Very low correlation (r = 0.324) was observed between micronucleus frequency in vitro and in vivo. Although micronucleus frequency at 2 Gy differed widely between tumours evaluated (mean MN/BNC was 0.224; range 0.08-0.416), no significant correlation was observed between this parameter and clinical outcome. The average increment of micronucleus frequency after 20 Gy amounted to 193% of spontaneous level (range 60-610%) and was independent of spontaneous micronucleation before radiotherapy. In contrast to in vitro results, these from in vivo assay seem to have a predictive value for radiotherapy of cervix cancer. The micronucleus increment in vivo that reached at least 117.5% of pretreatment value (first quartile for MN20 data set) correlated significantly with better tumour local control (P < 0.008) and overall survival (P < 0.045). Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (after fixed tested dose of 20 Gy) offers a potentially valuable approach to predicting individual radioresponsiveness and may be helpful for individualization of treatment strategy in advanced stage cervical cancer.     

巨块型宫颈癌肿瘤中心前程同步加量调强放疗止血效果的观察

目的 探讨肿瘤中心前程同步加量调强放疗治疗巨块型宫颈癌大出血的有效性和安全性。方法 21例伴有阴道大出血的巨块型宫颈癌患者,前程(前3次)给予肿瘤中心(宫颈大肿块边界内收2 cm的范围)同步加量放疗15 Gy分3次后给予常规分割剂量(2 Gy/次),肿瘤周边和盆腔全程采用常规分割照射剂量46 Gy分23次。同步化疗采用顺铂25 mg/m²每周方案。外照射结束后给予腔内放疗20 Gy/4次。结果 首程大剂量放疗后24 h内阴道出血量较前减少50%,1周内阴道出血渐止,止血率100%。结论 采用肿瘤中心同步加量调强放疗是巨块型宫颈癌阴道大出血的有效治疗措施。     

Effets tardifs de la radiothérapie externe sur la glande thyroïde

The thyroid is the purest endocrine gland in the body and is likely to produce clinically significant abnormalities after external radiotherapy. Functional clinical modifications after direct irradiation exceeding 30 Gy are essentially related to hypothyroidism which may be clinically overt or subclinical with normal serum free thyroxine levels and high thyrotropin concentrations; the risk of hyperthyroidism, silent thyroiditis and Hashimoto's disease is also increased. Secondary hypothyroidism related to irradiation of the hypothalamus and the pituitary gland may arise with doses over 40–50 Gy following treatment for brain and nasopharyngeal tumors — Morphological glandular modifications induced by radiotherapy are responsible for the appearance of benign adenomas, more rarely cystic degenerations and specially well differentiated papillary or follicular carcinomas among children and adults. After irradiation during childhood for benign or malignant tumors, thyroid cancers are more frequent, higher for younger children, and the relative excess risk is increased from 15.6-to 53-fold; tumors can belatedly occur, more than 35 years after initial therapy. Thereby, in order to limit excess morbidity, it is evident that long term supervision with careful clinical and biological evaluations is necessary for patients who previously received neck, upper mediastinum and pituitary radiation therapy.     

Incidence of hypothyroidism after irradiation of the neck with special reference to lymphoma patients. A retrospective and prospective analysis

Twenty-eight patients were studied prospectively in order to determine the incidence of hypothyroidism after mantle irradiation for malignant lymphoma. This group was compared with a historical group of 65 patients, among them 36 patients with malignant lymphoma. The mean follow-up was 30 months for the prospective group and 46 months for the retrospective group. The mean thyroid dose for irradiated malignant lymphomas in the prospective and the retrospective group was 45 Gy and 43 Gy respectively. For other tumors with neck irradiation (retrospective group) the mean thyroid dose was 53 Gy. There were no cases of clinical hypothyroidism in our study. As for subclinical hypothyroidism which is characterised by elevated TSH, the incidence was 22% in the prospective group and 3% in the retrospective group, i.e. 8/93 patients showed a hypothyroid dysfunction. Three of the 8 patients with subclinical hypothyroidism had undergone lymphangiography before radiotherapy. Due to the elevated iodine pool a lymphangiogram is considered as a risk factor for hypothyroidism as well as for hyperthyroidism, which we observed twice in the prospective group. Evaluation of the thyroid function before lymphangiography and irradiation as well as regular thyroid function studies during the follow-up are recommended in order to detect hypothyroidism in time.     

Interstitial and external radiotherapy in carcinoma of the soft palate and uvula

Forty-three patients, all male, with limited epidermoid carcinoma of the soft palate and uvula were treated by interstitial implant usually associated with external radiotherapy. Most patients received 50 Gy external irradiation to the oropharynx and neck followed by 20-35 Gy by interstitial iridium-192 wires using either guide gutters or a plastic tube technique. Twelve primary tumors and two recurrences after external irradiation alone had implant only for 65-75 Gy. Total actuarial local control is 92% with no local failures in 34 T1 primary tumors. Only one serious complication was seen. Overall actuarial survival was 60% at 3 years and 37% at 5 years but cause-specific survivals were 81% and 64%. The leading cause of death was other aerodigestive cancer, with an actuarial rate of occurrence of 10% per year after treatment of a soft palate cancer. Interstitital brachytherapy alone or combined with external irradiation is safe, effective management for early carcinoma of the soft palate and uvula but second malignancy is a serious problem.     

Intracavitary radiation treatment of nasopharyngeal carcinoma by the high dose rate afterloading technique

Sixty-four patients with nasopharyngeal carcinoma were treated by various combinations of external irradiation with intracavitary radiotherapy using the high dose rate afterloading technique. The afterloading intracavitary radiation (AIR) was given as a routine boost or for residual or recurrent disease. The external irradiation dose varied from 45 to 70 Gy, whereas the AIR dose ranged from 10-50 Gy, depending on the nature of the primary nasopharyngeal lesion. The results were quite encouraging, although the longest follow-up so far has only been just over 4 years. Of 13 such cases that received external radiotherapy plus AIR as primary treatment, 12 have survived. However, of the 9 cases who received AIR for local recurrence after external radiotherapy, only 5 survived. Of the total of 64 cases treated by AIR from June 1981 to May 1986, 54 are alive. No serious radiation sequelae have been observed. It can be concluded that AIR for nasopharyngeal carcinoma is indicated for boosting the dose to the nasopharyngeal cavity with appropriate reduction in external irradiation dose, and for residual or recurrent disease after primary external radiotherapy.     

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17–19–21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.     

早期鼻咽癌三维适形和常规外照射计划的剂量学评价(英文)

目的利用二维治疗计划系统对早期鼻咽癌常规和三维适形放疗(3D CRT)计划作剂量学比较,评估不同照射方法剂量分布的差异,为今后指导临床治疗提供剂量学的依据。方法选择22例早期鼻咽癌患者,用三维治疗计划系统对每例患者分别作出常规和3D CRT 计划设计,然后根据靶区覆盖率(V_(95))、正常组织受量(D_(50),D_(33)和 D_5等)和正常组织并发症发生率(NTCP)比较这两种计划。结果剂量学比较表明,常规和3D CRT 的 PTV_(nx70)、PTV_(nd60)、PTV_(nx60)、PTV_(nx50)的 V_(95)分别为98.22%和99.98%(P=0.06)、98.41%和99.63%(P=1.00)、98.22%和99.98%(P=0.03)、98.85%和99.63%(P=0.02)。保护正常组织方面:在3D CRT 和常规计划中,单侧腮腺的 D_(50)分别为51.91Gy 和64.30Gy(P=0.00),单侧颞颌关节 D_(50),49.98Gy 和64.47Gy(P=0.00),脊髓 D1cc,44.98Gy和48.09Gy(P=0.00)。结论 3D CRT 在亚临床靶区比常规方法有稍好的靶区覆盖率,3D CRT 治疗早期鼻咽癌的优势在于给予靶区相似剂量分布的前提下,可以比常规方法减少某些正常组织器官如腮腺、颞颌关节等照射剂量,减少它们的 NTCP。     

支气管动脉灌注加外照射治疗中晚期肺癌疗效观察

目的 :探讨同时应用支气管动脉灌注化疗和外放射治疗两种治疗方法治疗中晚期肺癌的疗效。方法 :采用Seldinger技术 ,经支气管动脉灌注化疗药物 :顺铂 6 0mg m2 ,阿霉素 4 0mg m2 ,丝裂霉素 6mg m2 或 5 FU 75 0mg m2 。每 3～ 4周灌注 1次 ,3～ 4次为 1个疗程。放疗于灌注后 10～ 15d进行。放射源为60 Co ,所有病例均为对穿照射。剂量DT2Gy 次 ,5次 周 ,总量DT5 0～ 6 0Gy 2 5～ 30次 ,共5～ 6周。结果CR 8例 (2 2 2 % ) ,PR 2 3例 (6 3 6 % ) ,S 3例 (8 6 % ) ,P 2例 (5 6 5 % )。总有效率CR PR为 (85 6 % ) ,2年生存率 2 7 8%。结论 :支气管动脉灌注加外放射治疗肺癌有协同作用 ,是目前治疗中晚期肺癌的一种安全、有效的方法     

Clinical study on radiotherapy combined with surgical treatment of 162 patients with cervical cancer

Objective: To compare the 5-year survival rates and complications of internal and external irradiation therapy combined with operation in patients with Ⅱ-Ⅲ period of cervical cancer.Methods: 162 cervical cancer patients after the whole palace resection pelvic lymphadenectomy were divided into three groups, and then accepted radiotherapy.The first group with 91 cases was accepted internal and external irradiation therapy before operation; the second group with 37 cases was given internal irradiation therapy before operation; the third group with 34 cases was given routine postoperative radiotherapy.External irradiation used 60Co irradiation or a linear accelerator, to the whole basin, and the irradiation dose of "B" point in preoperative radiotherapy was 26-30 Gy, in postoperative radiotherapy was 46-50 Gy; intraluminal brachytherapy used 192lr,the dose of "A" point was 5-15 Gy.Results: The 5-year survival rate of preoperative combined radiotherapy group was 78.0%(71/91), preoperative intracavitary radiotherapy group 64.9% (24/37), and postoperative radiotherapy group 35.3% (12/34).Comparing the 5-year survival rates of the preoperative combined and postoperative irradiation groups, there was significant difference (P＜0.05).The major complications were radioactive proctitis and cystitis, the complication incidences of three groups were 35.2% (32/91), 32.4% (12/37), 38.2% (13/34), respectively, and the differences were not statistically significant (P＞0.05).Conclusion: The intraluminal brachytherapy plus external irradiation can significantly increase the 5-year survival rate of patients with Ⅱa-Ⅲa stages, and the incidence of complications was not significant difference.     

Efficacy of radiotherapy for giant cell tumor of bone: given either postoperatively or as sole treatment

Purpose: The aim of this paper is to evaluate efficacy of radiotherapy for giant cell tumor of bone given either postoperatively or as sole treatment, and to assess prognostic factors for treatment outcome.

Methods and Materials: The study includes 37 patients. In 9 cases, soft tissue involvement was noted. Nonradical operation followed by radiotherapy was given to 23 patients, and 14 patients received irradiation only. Total dose of 39–64 Gy was delivered. The average follow-up was 5 years. Probability of local tumor control (LTC) depending on the treatment strategy was calculated, and prognostic factors were assessed.

Results: LTC was noted in 31 cases. Ten-year LTC for surgery with irradiation was 83% and 69% for radiotherapy alone; however, this difference was not statistically significant. For tumors smaller than 4 cm LTC probability was above 90%, and it decreased to less than 60% for tumors larger than 8.5 cm. No dose–response relationship has been found. In 7 cases, late normal tissue effect occurred.

Conclusions: Giant cell tumors of bone can be considered as radiosensitive and radiotherapy with total dose of 40–45 Gy seems to be an effective sole treatment especially for tumors smaller than 4 cm in diameter. For larger tumors, surgery combined with postoperative radiotherapy should be considered.     

External beam radiotherapy alone or combined with high-dose-rate intracavitary irradiation in the treatment of cancer of the esophagus: autopsy findings in 35 cases

Autopsy findings of 35 patients, treated with radiotherapy for an esophageal carcinoma, were reviewed. A residual tumor was seen at autopsy in 7 of 16 patients treated with high-dose-rate intracavitary irradiation following external irradiation, in 13 of 14 patients treated with external irradiation of 50 Gy or more, and in all 5 patients treated with external irradiation of less than 50 Gy. Incidence on lymph node metastasis, at autopsy, did not differ between the combined radiotherapy group and the external irradiation groups. However, it correlated with disease stage. It was observed in 11 of 17 patients with Stage 1 and Stage 2 disease, compared to 17 of 18 patients with Stage 3 and Stage 4 disease. Distant organ metastasis, at autopsy, also did not differ between the combined radiotherapy group and the external irradiation groups, and was also correlated with disease stage. It was found in 8 of 17 patients of the patients with Stage 1 and Stage 2 disease, compared to all 18 patients with Stage 3 and Stage 4 disease. Mean (average) survival was different between the patients treated by high-dose-rate intracavitary irradiation following external irradiation and those treated by external irradiation alone; 11.3 months in the 16 patients treated with combined therapy, as compared to 6.9 months in the 14 patients who received external irradiation of 50 Gy or more, and 3.6 months in the 5 patients who received external irradiation of less than 50 Gy.     

Plasmocytome solitaire osseux : expérience du service de radiothérapie de l’hôpital militaire d’instruction Mohammed-V de Rabat (Maroc)

PurposeThe primary objective was to determine in our department the progression-free survival rate of patients with solitary bone plasmocytoma and secondarily to evaluate its diagnostic, therapeutic and evolutionary aspects.Patients and methodsThis is a retrospective review of 12 patients monitored and treated in the radiotherapy department of the Mohammed-V military medical teaching hospital in Rabat for a solitary bone plasmocytoma between January 2012 and December 2018. The average age of our patients were 53.8 years old (range: 31-72 years old). Pain was the most common telltale sign. The site of the lesions was spinal in four cases, iliac in four cases, mandibular, ribal, humeral and at the level of the astragalus in one case respectively. All patients received radiotherapy. This irradiation was delivered alone in 60% of cases or associated with surgery in 40% of cases. The average dose of radiotherapy was 47.3 Gy (range: 45 to 50.4 Gy) and this was delivered by a modulated volumetric arc therapy technique in ten patients and conformal tridimensional radiotherapy in two patients.ResultsLocal control, defined by stability or radiological regression, was obtained in ten patients and four patients progressed to multiple myeloma, two of whom died. The average duration of follow-up was 51 months.ConclusionRadiation therapy is the standard treatment for solitary bone plasmocytoma. It ensures good local control in 90% of cases. The prognosis is affected by progression to multiple myeloma, which justifies rigorous monitoring after treatment and suggests a reflection on the exact place of chemotherapy.     

Hypothyroidism following cervical irradiation in the management of carcinoma of the nasopharynx and of the breast: a prospective study on eighty-four cases]

PURPOSE: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening. PATIENTS AND METHODS: From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxin was administered in case of hypothyroidism. RESULTS: All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P=0.002). CONCLUSION: Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended.     

Combined treatment with interstitial hyperthermia and interstitial radiotherapy in an animal tumor model

An interstitial hyperthermia system operating at 27 MHz has been developed at the Dr. Daniel den Hoed Cancer Center. To test this system in combination with interstitial radiotherapy and to study the interactions of interstitial radiotherapy and interstitial hyperthermia, animal experiments were performed using rhabdomyosarcoma type R1 transplanted in the flanks of female Wag/Rij rats. Using the 27 MHz system, it appeared feasible to obtain hyperthermic temperatures. In this experiment a thermal dose of 44 degrees C for 30 minutes was delivered by controlling the temperature at the periphery of the tumor to 44 degrees C. The interstitial heating applicators were inserted in four standard afterloading catheters implanted with a fixed spacing of 7 mm; the same catheters were used for the radioactive sources for interstitial radiotherapy treatment following the interstitial hyperthermia sessions. Interstitial radiotherapy was given by means of four Ir192 wires with an average activity of 4.5.10(7) Bq/cm. Minimum tumor doses of 20 to 115 Gy with a mean dose rate of 47 cGy/hour were applied. Interstitial hyperthermia alone resulted in a growth delay (GD1) of 6 +/- 2 days without significant reduction of tumor volume. The 50% tumor cure dose after interstitial radiotherapy alone was 95 +/- 9 Gy. Combination of interstitial hyperthermia and interstitial radiotherapy resulted in reduction of the 50% tumor cure dose to 48 +/- 13 Gy. The dose-effect data for cure for these modalities are compared to existing data for external irradiation and external hyperthermia in the same tumor model. It was found that the addition of hyperthermia to different modes of irradiation, that is, either to single dose or protracted radiotherapy, results in a common level of radiosensitivity through impaired repair of sublethal damage. This study demonstrates the feasibility of the 27 MHz heating system in achieving hyperthermic temperatures; in the combined modality experiments a thermal enhancement factor of 2.0 +/- 0.3 (mean +/- standard deviation) was observed.