373例食管癌患者三维技术放疗预后分析

目的 观察对食管癌患者采用三维技术放疗的长期疗效,并分析预后影响因素。方法 回顾性分析接受三维技术放疗食管鳞癌患者373例。其中三维适形放疗（3D-CRT）231例,调强放疗（IMRT）142例;单纯放疗202例,放化疗联合171例;累及野（IFI）照射249例,选择性淋巴引流区预防（ENI）照射124例;根治量50~60 Gy者60例,60~70 Gy者313例。Kaplan-Meier法计算总生存（OS）率、无进展生存（PFS）率,预后影响行Logrank单因素分析和Cox法多因素分析。结果 全组l、3、5年OS率和PFS率分别为69.4%、33.7%、22.9%和63.8%、32.8%、22.4%,中位OS和PFS分别为22.7个月（95%CI 18.6~25.4个月）和19.2个月（95%CI 16.7~21.3个月）。单因素分析显示,患者年龄、性别、肿瘤部位、不同三维技术、是否联合化疗、淋巴引流区是否预防照射、不同根治量对OS和PFS无影响（P>0.05）;T分期、N分期、TNM分期和GTV体积影响OS和PFS的因素（χ²=5.836~14.526,P<0.05）;多因素分析显示,N分期和GTV体积是影响OS和PFS的因素（χ²=5.345~12.216,P<0.05）。两个淋巴结区域转移患者的OS和PFS曲线均差于1个淋巴结区域转移者（χ²=4.467,4.169,P<0.05）。结论 食管癌患者采用三维技术放疗的长期疗效明显提高。N分期和肿瘤体积是影响患者预后的独立因素,淋巴结转移区域数与患者预后密切相关。     

Peripheral lymphocyte populations in patients treated with pelvic and mediastinal radiotherapy

Solid tumor bearing patients often show a large variety of immunologic alterations: increase in immune complexes number, reduced NK activity, decreased IL-2 production, T4/T8 reverse and s.o. Most literature data generally concern chemotherapy and/or radiotherapy pretreated patients, so it is difficult to relate the immunological alterations with either antineoplastic treatments or the disease itself. We tried to evaluate any possible alteration of immunological parameters in patients with solid neoplasms who underwent radiotherapy on mediastinum or pelvis. The aim was to detect any variation in peripheral lymphoid sub-populations (even per site of irradiation) and a possible activation of an immune therapy. The evaluable patients were 38 (12 treated with surgery). The minimum dose delivered was 5000 cGys through conventional fractionation. The immunological parameters (T, B, N, T4, T8, H/S) were evaluated before the treatment, at the end and every 2 months during follow-up. Cases were analyzed also per single irradiation volume. No statistically significant variation in immunological parameters was found, although suppressor activity was confirmed as prevailing in immune responsiveness of cancer patients. Thus any significant correlation between immunological state and disease evolution or response to treatment has still to be verified.     

立体定向适形放疗治疗原发性肝癌的近期疗效分析

目的 观察立体定向适形放疗治疗原发性肝癌的近期疗效.方法 28例原发性肝癌患者经Elscint twin flash 螺旋CT机定位后,用Leibinger三维放疗计划系统拟制放疗计划,在Varian直线加速器上实施治疗.平均随访时间为12个月.分析肿瘤反应率、放疗后无肝内肿瘤进展率及放疗后12个月生存率,观察治疗毒副作用.结果 放疗后肿瘤体积反应率为85.7%,放疗后12个月无肝内肿瘤进展率为38.4%,放疗后12个月生存率为70.5%.存活患者无晚期肝损伤.结论 立体定向适形放疗治疗肝癌的毒性较小,对提高肝内肿瘤的局部控制率有一定意义.     

96例脑胶质瘤术后放射治疗预后影响因素分析

目的探讨脑胶质瘤患者术后放射治疗的存活、预后影响因素。方法回顾性分析我院2009年3月至2013年11月收治的96例脑胶质瘤术后放射治疗患者,随访2~63个月,应用Kaplan-Meier法计算生存率及生存时间,Log-rank法做单因素分析,对单因素分析有意义的因素(P<0.05)采用Cox模型进行多因素分析。结果本组患者1、2、3年生存率分别为88.7%、68.5%、48.9%,生存时间中位数为37.51个月。单因素分析显示,放射治疗前卡氏功能状态(KPS)评分、年龄、病理分级及手术切除程度是影响胶质瘤患者预后的重要因素;多因素分析显示,年龄、放射治疗前KPS评分、手术切除程度是影响预后的独立因素。结论年龄>40岁、放射治疗前KPS评分>70分、手术全切可提高脑胶质瘤术后放射治疗患者的生存率。     

三维适形放射治疗局部晚期非小细胞肺癌长期生存分析

目的 评估三维适形放疗局部晚期非小细胞肺癌的长期疗效、放疗毒副反应及影响患者的预后因素。方法 2000年11月至2004年5月在河北医科大学第四医院接受根治性三维适形放疗并经病理或细胞学证实的Ⅲa/Ⅲb期非小细胞肺癌患者106例。46例接受单纯放射治疗;另60例接受化疗,其中同期化疗41例,序贯化疗19例。对相关临床指标进行单因素、多因素分析,并用预后指数模型综合评价放疗疗效。结果 全组患者治疗后,1、3、5年生存率分别为50.0%、22.2%、15.5%;1、3、5年局部控制率分别为80.2%、53.8%、32.7%;中位生存期12个月。其中单纯放疗、序贯放化疗及同期放化疗的中位生存期分别为10、12及13个月;Ⅲ_a与Ⅲ_b期患者中位生存时间分别为13、10.2个月。单因素分析结果显示,性别、治疗前卡氏评分、病理类型、锁骨上淋巴结、吸烟状况、治疗前血红蛋白值、N分期、瘤体最大直径、肿瘤体积、GTV大小及近期疗效为患者预后影响因素;多因素分析结果显示,吸烟状况、GTV大小及治疗前血红蛋白值为预后独立影响因素。全组≥2级放射性食管炎18例,占17.0%;≥2级放射性肺炎39例,占36.8%;≥3级血液学毒性反应11例,占10.4%。结论 三维适形放射治疗局部晚期非小细胞肺癌显示了较好的疗效,吸烟状况、GTV大小及治疗前血红蛋白值为非小细胞肺癌患者预后的主要影响因素。预后指数模型能够显著提高多指标联合的预测价值。     

One year of experience with alanine dosimetry in radiotherapy

Commercially available alanine dosimeters from different manufacturers were purchased for this study. The response of the detectors was evaluated with ⁶⁰Co gamma radiation in the dose range 0.2–200 Gy, using a small EPR spectrometer dedicated to dosimetry. The batch sensitivity, inter-specimen scattering and background signal for the different selection of dosimeters were evaluated. The usefulness of the alanine dosimetry system for clinical routine is illustrated by in vivo measurements during ¹⁹²Ir brachytherapy of cervix carcinoma.     

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

The purpose of this study was to evaluate the in vivo dose–response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35±0.2 Gy) than the calculated equivalent whole-body dose (0.07±0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2±0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1±0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.Quantification of chromosome aberrations in circulating lymphocytes is conventionally used to estimate the dose received by individuals accidentally exposed to ionising radiation. The observed frequency of dicentrics and centric rings is referred to a dose–response curve established in vitro, which provides the whole-body dose [1, 2]. When irradiation is heterogeneous over different parts of the body, only some lymphocytes are exposed. Because irradiated and unirradiated lymphocytes are mixed in the blood circulation, the dose received by the irradiated lymphocytes and consequently the dose delivered locally should be underestimated. Two mathematical models, Qdr and Dolphin''s deviation from the Poisson distribution, have been developed to assess the dose according to the fraction of exposed lymphocytes [3, 4]. Both models have been validated in vitro by mixing irradiated and unirradiated blood in different proportions [5]. These approaches have also been tested in vivo in accidental situations, with promising results [6, 7]. Furthermore, recent in vivo studies of cancer patients who had received 8 Gy of radiotherapy in a single fraction have shown that the derived partial-body dose obtained with both Qdr and Dolphin methods are in agreement with the doses estimated from the radiotherapy regimens [8].Cytogenetic assessment of cancer patients undergoing fractionated therapeutic irradiation would also be useful to evaluate the impact of the treatment on the yield of chromosome aberrations and on their distribution within the lymphocyte population. This could allow the evaluation of damage induced by such treatment in the patient''s circulating lymphocytes. Several studies have examined chromosome aberrations in blood samples from patients undergoing fractionated radiotherapy. These studies, which have used conventional cytogenetics, fluorescence in situ hybridisation (FISH) or both, showed a dose-dependent increase in the yields of aberrations, but with substantial interpatient variability [9–11]. The same variability in the rate of damage induced in lymphocytes during radiotherapy has been observed in other studies that used different measurements, such as premature chromosome condensation (PCC), micronuclei or γ-H2AX foci [12–14]. Explanations for these interpatient differences have suggested that damage yields after fractionated partial-body exposure do not depend only on the dose delivered locally, but may be also influenced by many other parameters, including individual variability in the response to ionising radiation, target field size or tumour localisation [9, 10, 12]. In fact, fractionated radiotherapy is a typical example of non-uniform exposure. During a session of radiotherapy, lymphocytes from the vascular pool may receive relatively small doses whereas those from the resident pool in the field may receive higher doses; both are ultimately mixed by the circulation in the following hours [15]. Furthermore, distribution of the lymphocyte pool may vary greatly within the human body; this implies that the geometry of irradiation may have a high impact on the proportion of vascular vs resident lymphocytes that may be irradiated. To measure the impact of radiotherapy treatment parameters on the aberration yields induced in peripheral lymphocytes, it is useful to study patients who have tumours in the same anatomical region. Therefore, to analyse the roles of the target field size and the dose rate relating to interpatient variability, we applied conventional cytogenetic methods to eight patients receiving fractionated radiotherapy for head and neck cancer. This anatomical region contains a high number of blood vessels and also a high number of lymph nodes. We evaluated the relation between the yield of dicentrics and centric rings measured in lymphocytes and the radiotherapy field size. We compared the dose estimate using cytogenetic methods with the physical doses obtained using calculations. Finally, we verified whether the test for deviation from Poisson distribution was able to detect the heterogeneity of the exposure after several fractions of radiotherapy.     

The role of MRI in patients with astrocytoma WHO II treated with fractionated stereotactic radiotherapy

Aim of this study was to evaluate the role of pre-therapeutic and follow-up MRI in the clinical treatment and outcome in patients with astrocytoma WHO grade II after fractionated stereotactic radiation therapy (FSRT). One hundred thirty-nine patients with histologically proven astrocytoma WHO grade II were treated with FSRT and retrospectively evaluated. All patients had follow-up MRI studies (Gd-DTPA-enhanced T1- and T2-weighted MR images). Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed on five potential MRI related prognosticators. Median follow-up was 3.8 years. Positive contrast enhancement (CM+) prior to FSRT proved to be a significant prognosticator for PFS and OS (p<0.01). Pre-therapeutic oedema on T2-weighted images and multifocality of contrast medium (CM) enhancement did not prove to be significant prognosticators. Also, diameter and volume of CM enhancement showed no significance on clinical outcome. Negative contrast enhancing (CM–) patients developing a de novo CM enhancement during follow-up showed a significantly worse clinical outcome compared with generally CM– patients (p<0.05). Pre-therapeutic CM enhancement and the development of CM-enhancing areas during follow-up are negative prognosticators for PFS and OS. They must be interpreted as signs of secondary malignity.     

Evaluation of quality of life and psychological response in cancer patients treated with radiotherapy

PURPOSE: The importance of the quality of life (QOL) and mental condition of patients being treated for cancer is now recognized. In this study, we evaluated QOL and mental condition in patients with cancer before and after radiotherapy. MATERIALS AND METHODS: The subjects were 170 patients who had undergone radiotherapy. The examination of QOL was performed using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), and mental condition (anxiety and depression) was examined using the hospital anxiety and depression scale (HADS). These examinations were performed at the start of radiotherapy and immediately after radiotherapy. RESULTS: The QOL score was slightly higher in all patients after the completion of radiotherapy than before the start of radiotherapy. In the palliative radiotherapy group, QOL score was significantly improved by treatment. Anxiety and depression were improved after radiotherapy. There was a correlation between the degrees of improvement of the HADS and QOL score. CONCLUSION: We could treat cancer patients by radiotherapy without reducing their QOL, and improvement in QOL was significant in the palliative radiotherapy group. Mental condition was also improved after radiotherapy.     

Prediction of pelvic control using MRI for patients with cervical carcinoma treated with radiotherapy

PURPOSE: To investigate the usefulness of MRI for predicting pelvic control (PC) of cervical cancer treated with radiation therapy (RT). MATERIALS AND METHODS: Forty-four cervical cancer patients treated with definitive RT were retrospectively analyzed. MRIs were completed before and after RT, and the longest diameter (LD) of the residual tumor was measured on post-RT MRI. Pathologic evaluation for residual tumor was also performed. Therapeutic response was assessed using MRI. Median follow-up time for the 44 patients was 34 months. The correlations between PC rate, MRI, and pathological findings were investigated. RESULTS: The 3-year PC rates of LD = 0 cm (n = 23) after RT, 0 < LD 2 cm (n = 6) were 85%, 80%, and 0%, respectively (p < 0.0001). There was no significant difference in PC according to the presence (n = 8) or absence (n = 36) of residue in the pathologic materials (3-year PC rate: 63% vs. 77%). Three-year PC rates according to therapeutic responses were 85% in complete response (n = 23), 72% in partial response (n = 18), and 0% in stable disease or progressive disease (n = 3) (p < 0.0001). CONCLUSION: MRI is useful for predicting PC in cervical cancer treated with RT, and LD greater than 2 cm after RT is a good marker for poor PC.     

Accuracy of set-up of thoracic radiotherapy: prospective analysis of 24 patients treated with radiotherapy for lung cancer

In thoracic radiotherapy, a number of factors hinder the use of portal films and electronic portal imaging devices for measuring field placement errors (FPEs). The aim of this study was to assess the accuracy of treatment set-up using simulator check films (SCFs) in radiotherapy for lung cancer. Prospective evaluation was performed on 24 patients. During their radiotherapy, patients returned to the simulator weekly for a minimum of four SCFs, for which the parameters from the original simulator planning film were set, positioning being achieved without fluoroscopy. A total of 96 SCFs were taken. FPEs in left-right (L-R) and superior-inferior (S-I) direction, as well as coronal rotational errors, were measured. The mean absolute FPE was 0.35 cm in the L-R axis and 0.43 cm in the S-I axis. Statistically, the FPEs in the S-I direction were greater than those in the L-R direction (p<0.001). A margin of 0.93 cm between the clinical target volume and the planning target volume would cover 95% of FPEs in the L-R direction, whilst a margin of 1.13 cm is needed for this degree of certainty in the S-I direction. Mean coronal rotational error was 1.6 degrees. Systematic errors were greater than random errors. This study demonstrated that the FPEs were within clinical tolerance (< or = 0.7 cm) in 84.9% of the measurements. The planning margins used in our clinical practice compare favourably with the FPEs in this study.     

同步加量调强放疗对颈胸上段食管癌患者长期预后的影响

目的:评估同步加量调强放疗(SIB-IMRT)对颈、胸上段食管癌患者长期预后的影响。方法:对2011年1月至2014年12月,接受IMRT的颈、胸上段食管癌的172例患者进行了回顾性分析。首先对全组患者的预后进行了单因素和多因素分析,依据患者照射方式,将全组患者分为常规IMRT(C-IMRT)和SIB-IMRT两组,应...     

Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy

Background and purpose

Acute bowel toxicity significantly affects the quality of life of patients treated with pelvic radiotherapy. This study was performed to assess whether pretreatment with famotidine can reduce acute radiation toxicities in patients undergoing radiotherapy for prostate cancer.

Patients and methods

Between April 2012 and February 2013, 36 patients undergoing radiotherapy for prostate cancer were enrolled to receive either placebo or famotidine. The patients received external-beam radiotherapy up to 70 Gy at daily fractions of 1.8–2 Gy (5 days/week). Oral famotidine 40 mg (80 mg/day) or placebo was administered twice daily (4 and 3 h prior to each radiotherapy fraction). Bowel and bladder acute toxicities were evaluated weekly during radiotherapy and once thereafter according to RTOG grading criteria.

Results

Famotidine was well tolerated. No grade III or higher acute toxicities were noted in the two groups. Grade II rectal toxicity developed significantly more often in patients receiving placebo than in patients receiving famotidine (10/18 vs. 2/16, p?=?0.009). Moreover, no rectal bleeding occurred in the famotidine group, while 5 patients in the placebo group experienced rectal bleeding during treatment (p?=?0.046). The duration of rectal toxicity in the radiotherapy course was also reduced in the famotidine group (15.7 vs. 25.2 days, p?=?0.027). No significant difference between the two groups was observed in terms of urinary toxicity.

Conclusion

We demonstrated for the first time that famotidine significantly reduces radiation-induced injury on rectal mucosa representing a suitable radioprotector for patients treated with radiotherapy for prostate cancer.     

Radiation-related eosinophilia. Correlation with delayed hypersensitivity, lymphocyte count, and survival in patients treated by curative radiotherapy.

Abdominal irradiation may produce eosinophilia. The relationship between radiation-related eosinophilia (RRE), reactivity to 2-4 dinitrochlorobenzene (DNCB), lymphocyte count, and prognosis was evaluated in 98 patients irradiated for tumors below the diaphragm. Forty-two per cent manifested RRE and 62% reacted to DNCB. Fifteen of 19 (79%) reactors who had RRE were disease-free at 6 months. Fourteen of 22 (64%) nonreactors who had RRE and 26 of 42 (62%) DNCB reactors without RRE were controlled. Fourteen of 15 (93%) nonreactors without RRE had disease at 6 months. Those who had RRE had double the median survival of those who did not.     

The first patients treated with MR-CBCT soft-tissue matching in a MR-only prostate radiotherapy pathway

IntroductionMagnetic Resonance (MR)-only radiotherapy for prostate cancer has previously been reported using fiducial markers for on-treatment verification. MR-Cone Beam Computed Tomography (CBCT) soft-tissue matching does not require invasive fiducial markers and enables MR-only treatments to other pelvic cancers. This study evaluated the first clinical implementation of MR-only prostate radiotherapy using MR-CBCT soft-tissue matching.MethodsTwenty prostate patients were treated with MR-only radiotherapy using a synthetic (s)CT-optimised plan with MR-CBCT soft-tissue matching. Two MR sequences were acquired: small Field Of View (FOV) for target delineation and large FOV for organs at risk delineation, sCT generation and on-treatment verification. Patients also received a CT for validation. The prostate was independently contoured on the small FOV MR, copied to the registered CT and modified if there were MR-CT soft-tissue alignment differences (MR-CT volume). This was compared to the MR-only volume with a paired t-test. The treatment plan was recalculated on CT and the doses compared. Independent offline CT-CBCT matches for 5/20 fractions were performed by three therapeutic radiographers using the MR-only contours and compared to the online MR-CBCT matches using two one-sided paired t-tests for equivalence within ±1 mm.ResultsThe MR-only volumes were significantly smaller than MR-CT (p = 0.003), with a volume ratio 0.92 ± 0.02 (mean ± standard error). The sCT isocentre dose difference to CT was 0.2 ± 0.1%. MR-CBCT soft-tissue matching was equivalent to CT-CBCT (p < 0.001), with differences of 0.1 ± 0.2 mm (vertical), ?0.1 ± 0.2 mm (longitudinal) and 0.0 ± 0.1 mm (lateral).ConclusionsMR-only radiotherapy with soft-tissue matching has been successfully clinically implemented. It produced significantly smaller target volumes with high dosimetric and on-treatment matching accuracy.Implications for practiceMR-only prostate radiotherapy can be safely delivered without using invasive fiducial markers. This enables MR-only radiotherapy to be extended to other pelvic cancers where fiducial markers cannot be used.     

乳腺癌保乳术后放射治疗的疗效观察

目的观察乳腺癌保乳术后放射治疗的疗效和美观效果。方法109例保乳术后在我科接受全乳外照射和瘤床加量(boost)放疗,79例应用高剂量率插植技术,T1肿瘤用单排插植,针距为1.5cm,T2以上肿瘤用双排或三排插植。针距间单次剂量(DB)10～12Gy,靶区周边剂量为85%DB。30例采用电子线常规外照射15Gy。全乳照射应用6MV直线加速器,采用双切线半野照射技术,靶区剂量为45～52Gy(平均48.6Gy)。采用医生评分与患者问卷方法评价美观效果。结果全组109例应用KaplanMeier方法统计5年实际生存率为93.8%。局部复发率为6.5%。全组无放射性溃疡发生,5例出现位于插植针孔周围急性皮肤炎症。在经临床随访体检的75例中,医生打分和患者自评满意度为优的比例分别为87%和81%,无统计学意义(P>0.05)。48例经组织间插植加量放疗;27例经电子线外照加量放疗。两组满意度医生总评为优的患者比例分别为81.2%和85.2%,差异无统计学意义(P>0.05)。结论乳腺癌保乳术后放疗可降低局部复发率,并发症少。不同的瘤床加量放疗方法不影响美观效果。     

Acute radiation reaction and local control in breast cancer patients treated with postmastectomy radiotherapy

Background

We have investigated the variation of acute radiation reactions in medium-risk patients with postmastectomy radiotherapy with regard to a possible correlation between radiation oeaction of normal tissues and local tumor control.

Material and Methods

From 1985 through 1991, a total number of 194 patients received postmastectomy radiotherapy for breast cancer pT1-2pN0-2M0 at the University of Halle-Wittenberg. The lymphatics were irradiated by an anterior 9-MV photon field and the chest wall by an individually shaped anterior field with 9-MV electrons. Both fields received single doses of 2 Gy 5 times weekly up to a total dose of 44 Gy to the chest wall and 50 Gy to the lymphatics. All patients were routinely evaluated once weekly during radiotherapy for acute side effects by one examiner. Skin erythema was classified as mild, moderate or severe, esophagitis as being present in form of dysphagia or not and pneumonitis, if present, as asymptomatic (visible only on repeated chest X-rays) or clinically symptomatic. A differential blood count was also carried out once weekly. For this analysis, the records of all patients were retrospectively reviewed. The median follow-up at the time of analysis was 4.2 years.

Results

Of the patients, 98 (51%) had a mild, 53 (27%) moderate and 43 (22%) a severe erythema. Furthermore, 38 patients (20%) had signs of esophagitis, 13 (7%) had asymptomatic and 26 (13%) symptomatic pneumonitis. Patients with severe erythema or erythema plus esophagitis and pneumonitis had a more pronounced decrease in lymphocyte count during treatment than patients with mild erythema: the lymphocyte nadir was 0.14 vs 0.73 Gpt/l in patients with severe vs mild erythema, and 0.36 vs 0.69 Gpt/l in patients with erythema plus esophagitis plus pneumonitis vs patients with erythema only, p<0.05. Of the patients, 44 (22%) developed chronic side effects, mostly arm edema. There was no correlation between acute and late effects. An overall number of seven local recurrences (3.6%) occurred. The risk of developing a local recurrence within 5 years after treatment was 0% in patients with severe erythema or erythema plus esophagitis/pneumonitis vs 7% in patients with mild erythema only; this difference was marginally significant, p=0.055.

Conclusions

This analysis showed a trend towards better local control in patients with severe acute radiation reaction of normal tissue. The data support a recent publication by Dahl and coworkers showing a linkage between acute radiation reaction of normal tissue and tumor response in patients with preoperative radiotherapy for rectal cancer. The correlation between acute normal tissue reaction and local control might be explained by interindividual variations in the intrinsic, genetically determined radiosensitivity. However, local factors might also be involved, e. g. induction of a cytokin cascade in cases of acute reactions in normal tissues.     

Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy

Background and purpose

Vascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer.

Patients and methods

The association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496 prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5’-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program.

Results

Within a median follow-up time of 80 months, 44 patients (9?%) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (??2578C > A, ??2489C > T, ??1498C > T, ??634G > C, ??7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95?%CI 1.48–9.90, p?=?0.006); for carriers of 2 copies, the HR was 4.85 (95?%CI 1.72–13.6; p?=?0.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95?%CI 1.38–9.55, p?=?0.009); in patients carrying 2 copies, the HR was 4.72 (95?%CI 1.64–13.6, p?=?0.004).

Conclusion

Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy.