Intensity-modulated radiotherapy for pituitary adenomas: the preliminary report of the Cleveland Clinic experience

PURPOSE: Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of pituitary adenomas. However, there have been few published data on the short- and long-term outcomes of this treatment. This is the initial report of the Cleveland Clinic's experience. METHODS AND MATERIALS: Between February 1998 and December 2003, 34 patients with pituitary adenomas were treated with IMRT. A retrospective chart review was conducted for data analysis. RESULTS: With a median follow-up of 42.5 months, the treatment has proven to be well tolerated, with performance status remaining stable in 90% of patients. Radiographic local control was 89%, and among patients with secretory tumors, 100% had a biochemical response. Only 1 patient required salvage surgery for progressive disease, giving a clinical progression free survival of 97%. The only patient who received more than 46 Gy experienced optic neuropathy 8 months after radiation. Smaller tumor volume significantly correlated with subjective improvements in nonvisual neurologic complaints (p = 0.03), and larger tumor volume significantly correlated with subjective worsening of visual symptoms (p = 0.05). New hormonal supplementation was required for 40% of patients. Younger patients were significantly more likely to require hormonal supplementation (p = 0.03). CONCLUSIONS: Intensity-modulated radiation therapy is a safe and effective treatment for pituitary adenomas over the short term. Longer follow-up is necessary to determine if IMRT confers any advantage with respect to either tumor control or toxicity over conventional radiation modalities.     

The efficacy of conventional radiation therapy in the management of pituitary adenoma

Purpose: To evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas.

Methods and Materials: We reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1–14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed.

Results: Mass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushing’s disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushing’s disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation.

Conclusion: We conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.     

Long-term outcomes of radiotherapy for pituitary adenomas

PURPOSE: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). METHODS AND MATERIALS: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). RESULTS: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p = 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. CONCLUSIONS: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.     

68例垂体瘤放射治疗的临床分析

背景与目的：垂体瘤是比较常见的颅内肿瘤,主要的治疗方法有手术,放射治疗等,本文比较不同治疗方法对垂体瘤的效果。以及对不同类型垂体瘤的疗效。方法：从1980年3月到1992年1月,68例垂体瘤行放射治疗,37例不分泌激素,52例为术后放射,16例为单纯放射,均为常规放射,中位剂量为49.7Gy(25.6-65Gy),采用^60Coγ线照射45例,8MVX线照射10例,18MVX线照射13例。结果：全组总的5年生存率为94.1%,10年生存率76.8%,全组总的局部控制率5年和10年分别为94%和89.1%。男性5年和10年的局部控制率89.7%,89.7%,女性分别为97%和88.4%,P=0.2985,从照射剂量来看,50Gy以下和50Gy以上总的局部控制率分别为82%和94%,两者比较P=0.1796。三野及旋转治疗略高于双颞侧野照射,激素分泌,病理类型以及各种射线之间均无差异。8例死于肿瘤复发,照射剂量在50Gy以下的39例。仅1例发生并发症,而照射剂量在50Gy以上的29例病人,有5例发生并发症,P值为0.0058,有显著性差异。结论：垂体瘤的照射剂量宜在45-50Gy,最好能采用三野照射。     

垂体腺瘤中黏蛋白1的表达与肿瘤侵袭性的关系

目的 探讨垂体腺瘤中黏蛋白1（MUC1）的表达与肿瘤侵袭性的关系.方法 采用免疫组织化学法检测26例侵袭性垂体腺瘤和29例非侵袭性垂体腺瘤患者肿瘤组织中MUC1的表达.结果 侵袭性垂体腺瘤组织中MUC1高表达,阳性率为76.92％（20/26）;非侵袭性垂体腺瘤组织中MUC1为弱阳性表达或不表达,阳性率为27.57％（8/29）,两者差异有统计学意义（x2=13.35,P＜ 0.01）.功能性垂体腺瘤组织中MUC1阳性率为44.82％（13/35）,非功能垂体腺瘤中MUC1阳性表达率为75.00％（15/20）,两者差异无统计学意义（x2=6.13,P＞ 0.01）.结论 MUC1在侵袭性垂体腺瘤组织中的表达及分布特点可作为垂体腺瘤侵袭性的辅助鉴别诊断指标,有可能作为垂体腺瘤免疫治疗的靶抗原.     

Gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience

PURPOSE: To evaluate the efficacy and complications of stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas (NFA). METHODS AND MATERIALS: This was a retrospective review of 62 patients with NFA undergoing radiosurgery between 1992 and 2004, of whom 59 (95%) underwent prior tumor resection. The median treatment volume was 4.0 cm(3) (range, 0.8-12.9). The median treatment dose to the tumor margin was 16 Gy (range, 11-20). The median maximum point dose to the optic apparatus was 9.5 Gy (range, 5.0-12.6). The median follow-up period after radiosurgery was 64 months (range, 23-161). RESULTS: Tumor size decreased for 37 patients (60%) and remained unchanged for 23 patients (37%). Two patients (3%) had tumor growth outside the prescribed treatment volume and required additional treatment (fractionated radiation therapy, n = 1; repeat radiosurgery, n = 1). Tumor growth control was 95% at 3 and 7 years after radiosurgery. Eleven (27%) of 41 patients with normal (n = 30) or partial (n = 11) anterior pituitary function before radiosurgery developed new deficits at a median of 24 months after radiosurgery. The risk of developing new anterior pituitary deficits at 5 years was 32%. The 5-year risk of developing new anterior pituitary deficits was 18% for patients with a tumor volume of < or = 4.0 cm(3) compared with 58% for patients with a tumor volume >4.0 cm(3) (risk ratio = 4.5; 95% confidence interval = 1.3-14.9, p = 0.02). No patient had a decline in visual function. CONCLUSIONS: Stereotactic radiosurgery is effective in the management of patients with residual or recurrent NFA, although longer follow-up is needed to evaluate long-term outcomes. The primary complication is hypopituitarism, and the risk of developing new anterior pituitary deficits correlates with the size of the irradiated tumor.     

垂体腺瘤组织p16基因表达的初步研究

背景与目的:近年研究表明,抑癌基因p16表达缺失及失活在人类多种肿瘤发生发展过程中发挥重要作用,但其与垂体腺瘤之间的关系研究甚少,本研究旨在探讨垂体腺瘤中p16基因表达情况及其与肿瘤临床病理特点、侵袭性、复发之间的关系。方法:用RT-PCR、Westernblot方法分别检测70例垂体腺瘤及10例正常脑组织中p16mRNA、p16蛋白表达情况,并结合临床病理进行探讨。结果:74.3%(52/70)垂体腺瘤中的p16mRNA、p16蛋白表达缺失或低下,侵袭性腺瘤、复发腺瘤p16表达缺失率均分别高于非侵袭腺瘤及非复发腺瘤,但统计学处理各组间无显著差异(P>0.05);p16表达缺失肿瘤的平均直径为(22.1±7.2)mm,明显大于阳性表达肿瘤的直径(8.1±4.5)mm(P<0.01)。此外,p16基因表达与垂体腺瘤其它临床病理特点均无显著相关。结论:在垂体腺瘤中存在较普遍的p16基因转录抑制及表达低下,其失活可能在垂体腺瘤形成早期发挥重要作用,并对肿瘤生长及生物学行为演变起一定促进作用。     

垂体腺瘤经蝶入路显微手术适应证选择及疗效

 目的:报告我科1986年7月～1996年10月经蝶显微手术治疗垂体腺瘤376例,女性239例,男性137例,年龄13～67岁,平均38.9岁.其中大腺瘤152例(40.4%),微腺瘤224例(59.6%).方法:均经CT扫描或MRI确诊,手术采取经唇下-鼻中隔-蝶窦入路或经鼻前庭-鼻中隔-蝶窦入路两种方式行肿瘤切除术.结果:术后无死亡.308例获长期随访(平均3.5年),258例(83.8%)恢复良好.52例(16.9%)肿瘤有复发,需行再次手术,或采用药物、放疗或放射外科治疗.结论:垂体腺瘤采取经蝶显微外科治疗是-种安全、有效的方法.     

Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas

Aberrant hypermethylation of CpG islands in the promoter region plays a causal role in the inactivation of various key genes involved in the cell cycle regulatory cascade, which could result in a loss of cell cycle control. The aim of the present study was to examine in more detail the prevalence and role of the promoter methylation of genes with a proven involvement in the cell cycle regulation of pituitary adenomas, since their tumorigenesis has not yet been clearly defined. We profiled the CpG island methylation status of a series of well-characterized cell cycle regulation genes: the RB1, p14 ^ARF , p15 ^INK4b , p16 ^INK4a , p21 ^Waf1/Cip1 , p27 ^Kip1 , and p73 genes, in 34 pituitary adenomas as determined by a methylation-specific polymerase chain reaction assay. Promoter hypermethylation of the RB1, p14 ^ARF , p15 ^INK4b , p16 ^INK4a , p21 ^Waf1/Cip1 , p27 ^Kip1 , and p73 genes was detected in 12 (35%), 2 (6%), 11 (32%), 20 (59%), 1 (3%), 0 (0%), and 4 (12%) of the adenomas, respectively. In total, 88% (30 of 34) of the adenomas displayed methylation of at least one of such cell cycle regulatory genes, especially methylation of the member genes of the RB1 pathway (29 of 34; 85%). Promoter hypermethylation of p15 ^INK4b coincided with RB1 and/or p16 ^INK4a methylation, whereas RB1 and p16 ^INK4a methylations tended to be mutually exclusive (p = 0.0048). Furthermore, promoter hypermethylations of p14 ^ARF , p21 ^Waf1/Cip1 , and p73 (not belonging to the member genes of the RB1 pathway) were also coincident with RB1 and/or p16 ^INK4a methylation except in one p73 methylated case. In contrast, none of the clinicopathological features, including the cell proliferation index, was significantly correlated with any particular methylation status. Our results suggested that aberrant hypermethylation of the key cell cycle regulatory genes occurs at a relatively high frequency in pituitary adenomas, especially in RB1 pathway genes with promoter hypermethylation of the p16 ^INK4a gene being the most common deregulation. We further obtained evidence to indicate that RB1 and p16 ^INK4a methylations tended to be mutually exclusive, but did occasionally coincide with other cell cycle regulation gene methylations.     

IN SITU PCR AND IMMUNOHISTOCHEMICAL STUDIES ON p16 GENE IN PITUITARY ADENOMAS

The alteration of pl6, a member of cyclin-dependentkinase inhibitor mdly, has been intensively investigatedby the aPProaches of molecular biology. The geneencoding pl6 protein, named Multiple Tumor SuPPressorl (MTS 1), was reported to be homozygously deleted in alarge number of tumor cell lines.[l'ZI While these datasuggested possible wide and essential involvement of pl6deletion in multiple types of human tUmors, pl6 genedeletion in primary tumors has been found much lesspredominant than…     

High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients

To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT).

Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6–60 months).

Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of ≥ late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of ≥ late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively.

These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be significantly reduced compared with what has been observed with conventional three-dimensional conformal radiotherapy techniques. Short-term PSA control rates seem to be at least comparable to those achieved with three-dimensional conformal radiotherapy at similar dose levels. Based on this favorable risk:benefit ratio, IMRT has become the standard mode of conformal treatment delivery for localized prostate cancer at our institution.     

内镜辅助下经鼻蝶窦垂体瘤切除术后生存质量的多因素临床研究

背景与目的:现代医学模式要求更全面的指标来评价手术疗效,而生存质量已成为其中一个重要标准。本文探讨与内镜辅助下经鼻蝶窦垂体瘤切除术后患者生存质量相关的多种因素,为全面评估手术疗效提供依据。方法:分析116例垂体瘤患者临床资料、影像学及病理检查结果,采用生存质量量表随访近5年的相关数据,并经计算机统计分析。结果:各种类型的垂体腺瘤术后生存质量较满意,不同分型间其生存质量统计无明显差异,而肿瘤越大,生存质量越低(P<0.01);侵袭性大、手术切除程度下降、复发的垂体瘤患者术后生存质量显著降低(P<0.01)。逐步回归分析方程为:Y=120.2097-1.7140x4-8.4210x5-9.6650x6,R=0.7944;Cox模型分析示:垂体瘤大小、垂体瘤侵袭性、手术切除程度是影响生存质量的主要因素。结论:术前MRI示垂体瘤大小,侵袭程度,术中手术切除程度,可预测术后生存质量;尽量行肿瘤全切术、早期发现复发可望提高患者生存质量。     

High-dose reirradiation with intensity-modulated radiotherapy for recurrent head-and-neck cancer: Disease control,survival and toxicity

Purpose

To evaluate disease control, survival and severe late toxicity after high-dose fractionated reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent head-and-neck cancer.

Materials and methods

Sixty consecutive patients were reirradiated with IMRT between 1997 and 2011. The median prescribed dose was 70 Gy in 35 daily fractions until 2004 and 69.12 Gy in 32 daily fractions thereafter. The median cumulative dose was 132 Gy. Sixty-seven percent of patients had non-metastatic stage IV disease. Surgery prior to reirradiation and concomitant systemic therapy was performed in 13 (22%) and 20 (33%) patients, respectively.

Results

Median follow-up in living patients was 18.5 months. Actuarial 1-, 2- and 5-year locoregional control was 64%, 48% and 32%, respectively. Median overall (OS) and disease-free survival was 9.6 and 6.7 months, respectively. Actuarial 1-, 2- and 5-year OS was 44%, 32% and 22%, respectively. Seventeen (27%) and 2 (3%) patients had grade 3 and 4 acute toxicity, respectively. Cumulative incidence of late grade ? 3 toxicity was 23%, 27% and 66% at 1, 2 and 5 years, respectively. In 4 patients, death was attributed to toxicity: fatal bleeding (n = 2), aspiration pneumonia (n = 1) and skin necrosis (n = 1).

Conclusions

High-dose fractionated reirradiation with IMRT offers 5-year disease control and OS in recurrent head-and-neck cancer for 1/3 and 1/4 patients, respectively. Severe late toxicity after 1–2 and 5 years occurs in 1/4 and 2/3 patients, respectively.     

垂体瘤立体定向放射外科治疗临床观察

 目的　分析报告微小垂体腺瘤 SRS治疗观察结果。方法　 94年 8月至 98年 8月对1 8例经挑选的垂体瘤实施了 SRS治疗。中位肿瘤最大直径为 1 0 mm,中位年龄 34岁 ,中位肿瘤边缘剂量 2 0 Gy。结果　 87.5% (1 4/1 6)的病例获得临床症状改善 ,1 2 .5% (2 /1 6)无变化。影象学观察结果显示 37.5% (6/1 6)肿瘤缩小 ;56.3% (9/1 6)肿瘤体积无变化。 2 1 .4% (3/1 4)激素水平在 SRS治疗后 1年降至正常 ,57.1 % (8/1 4)激素水平有所下降 ,2 1 .4% (3/1 4)未变。结论　肿瘤周边剂量1 8～ 2 2 Gy为安全有效的治疗剂量。建议谨慎掌握对年轻病人 SRS剂量 ,对体积较大、有明显侵袭性、紧贴视神经的垂体瘤应以显微外科或者立体定向分次照射为首选治疗手段。     

Intraoperative optical identification of pituitary adenomas

Introduction The main goals of transsphenoidal pituitary surgery are total removal of pituitary adenomas (PAs) and preservation of normal pituitary functions. Achieving these goals is dependant upon the precise localisation of PAs during surgery, particularly secreting microadenomas. However, some microadenomas are invisible on preoperative imaging and during surgery, leading some surgeons to perform total hypophysectomy in many patients to achieve cure at the expense of panhypopituitrism. We have examined optical detection systems to identify PAs intraoperatively. This paper reports our preliminary findings. Methods A prospective observational study design. Technique Patients were given 20 mg/kg body weight 5-aminolevulinic acid (ALA) mixed in 30 ml of orange juice, orally 3 h before surgery. Surgery was performed in the supine position, under image guidance, through the right nostril using Storz 0 degree endoscope assisted with microsurgery as required. The endoscope was attached to photodiagnostic filters (PD) allowing switching the light from white to blue at the flick of a foot pedal. After the dura of the floor of the sella was incised a laser probe was inserted into the pituitary gland to identify the ALA-induced protoporphyrin IX spectroscopy at 632 nm, using an optical biopsy system (OBS). Once the adenoma was identified by the OBS it was exposed and examined by the PD system to detect fluorescence. The PA was removed and its type was confirmed by histopathology and correlated to the OBS and PD system findings. Patients Thirty consecutive patients were studied: 14 were non-functioning macroadenomas (NFA), 12 were secreting PAs and 4 pituitary cysts. The secreting PAs were GH (2), ACTH (3), prolactin (2) and gonadotrophins (5). Six were microadenomas (3 ACTH, 1 GH, 2 prolactin) and 20 were macroadenomas, of which 12 were invading macroadenomas. Twenty-four of these were examined by the OBS and the PD systems and six were examined by the PD system only. The true positive (sensitivity) of the PD and OBS systems were 80.8% (21/26) and 95.5% (21/22) respectively. The true negative (specificity) of PD and OBS were 75% (3/4) and 100% (2/2) respectively. The false negative rate of PD was 19.2% (5/26) and for OBS was 4.5% (1/22), while the false positive rate for PD was 25% (1/4) and for OBS was 0. Conclusion Intraoperative optical identification of pituitary adenomas is a feasible and reliable way to localize pituitary adenomas during transsphenoidal surgery and it may lead to improved cure rate and preservation of normal pituitary functions.     

Tyrosine positron emission tomography and protein synthesis rate in pituitary adenoma: Different effects of surgery and radiation therapy

Introduction

Positron emission tomography (PET) using amino acid tracers is able to establish biochemical tumour characterization in vivo. The use of PET in the follow-up of non-functioning pituitary adenomas (NFA) and growth hormone producing pituitary adenomas (GHA) after surgery and radiation treatment is not yet clear.

Methods

To determine the value of PET before and after transsphenoidal neurosurgery in NFA and GHA, we investigated 12 patients with pituitary adenoma (9 NFA and 3 GHA) before and 4 months after surgery with magnetic resonance imaging (MRI) and tyrosine PET (TYR-PET). Three years after radiation therapy TYR-PET was used to document residual activity in 6 of these patients (4 NFA- and 2 GHA). Tumour size was quantified by computerized MRI measurements. In TYR-PET, tumour activity was assessed by computerized measurements of the hot spot and by determination of protein synthesis rate (PSR).

Results

In response to surgery, MRI showed a median tumour volume reduction of 58% (P < 0.01). TYR-PET demonstrated 62% volume reduction (P < 0.02), but no change in PSR (P > 0.30). After radiation therapy the MRI-volumes of the residual pituitary adenomas did not change but the volume of the hot spot on TYR-PET-imaging was reduced by 58% (P = 0.02), and PSR decreased in 5 of 6 patients (P = 0.12).

Conclusion

Amino acid PET tumour activity is reduced parallel with MRI volume changes after surgery. The decrease in TYR-PET activity after radiation therapy, despite unaltered MRI tumour volume, supports the concept that it is possible to follow biological tumour activity with this technique. The diagnostic merit of this tracer technique, predicting pituitary adenoma re-growth, needs to be validated in a large prospective study.     

Radiotherapy for rectal cancer is associated with reduced serum testosterone and increased FSH and LH

PURPOSE: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. METHODS AND MATERIALS: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. RESULTS: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. CONCLUSIONS: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.     

Long-term survival and risk of second cancers after radiotherapy for cervical cancer

PURPOSE: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. METHODS AND MATERIALS: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. RESULTS: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. CONCLUSIONS: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.