Radiation therapy of intrathoracic paraaortic lymph node metastases. Three-dimensional treatment planning

The elaboration of a CT-based three-dimensional radiation therapy plan is described, which is applicable for any location and extension of intrathoracic paraaortic lymph node metastases. Calculations for high energy photon beams from a 15 MeV linear accelerator have been performed. The treatment plan enables a high radiation dose in the target volume and adequate sparing of the spinal cord.     

宫颈癌常规照射野对盆腔淋巴结覆盖性研究

的距离.定义血管壁至射野距离在15～20 mm为射野大小充分,<15 mm为射野过小, 20 mm为射野过大.结果 上界98%患者有髂总淋巴结遗漏,2%患者射野过大;14%患者至少有一侧髂内、外淋巴结遗漏.侧界41%患者有髂外淋巴结遗漏,11%患者射野过大.前界43%患者有髂外淋巴结遗漏,25%患者射野过大.结论 根据骨性标记定义常规盆腔照射可能带来淋巴结靶区遗漏(特别是髂内外淋巴结),用CT或MRI图像勾画淋巴结靶区可以个体化设计照射野,以保证淋巴引流区包括在照射野内.     

Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma

BACKGROUND: The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma. METHODS: Uninvolved tumor-draining lymph nodes (TDLN) (n=158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)-treated patients, and 19 chemoradiation (CR)-treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon-gamma (IFN-gamma) production. Lymphocyte subsets in peripheral blood also were assessed. RESULTS: TDLNs from CR-treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT-treated patients (P values ranged from <0.05 to <0.01). TDLNs from CR-treated patients were enriched in activated-type CD4+ cells (HLA-DR+, CD134+, CD62L-, and CD25+ at an intermediate expression level; P values ranged from <0.05 to <0.01) and activated-type CD8+ cells (CD62L-, P<0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of na?ve-type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P<0.01 and <0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN-gamma. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy-induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood. CONCLUSIONS: To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma.     

Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes

Purpose: To evaluate local tumor control, cause-specific survival, patterns of relapse, and toxicity in patients with cervical cancer and positive para-aortic lymph nodes treated with radiation therapy alone.Methods: This is a retrospective chart review of 43 patients with cervical cancer and biopsy-proven positive para-aortic lymph nodes treated with radiation therapy treated from 1965 to 1993. There were 15 patients with clinical Stage I disease, 12 with Stage II, and 16 with Stage III. Patients were treated with external irradiation to the pelvis and para-aortic regions combined with brachytherapy. None received chemotherapy.Results: The 5-year overall survival rate was 32% and the median overall survival was 2.2 years. The 5-year cause-specific survival rate was 49% and the median cause-specific survival was 2.7 years. The cause-specific survivals at 5 years were 47% for Stage I, 64% for Stage II, and 46% for Stage III. Tumor recurrence occurred in 20 patients. The sites of recurrence were in the pelvis only in 3, the pelvis and distant metastasis in 9, and distant metastasis only in 8 patients. Severe, grade 3 complications occurred in 2 patients. One patient developed an enterovaginal fistulas and 1 developed radiation myelitis.Conclusion: Pelvic and para-aortic irradiation and brachytherapy resulted in a 49%, 5-year, cause-specific survival. Clinical tumor stage did not effect outcome. The majority of relapses occurred at distant sites. Toxicity was acceptable. Systemic chemotherapy should be considered as adjunctive therapy for these patients.     

Radiation therapy of stage I breast cancer: analysis of treatment technique accuracy using three-dimensional treatment planning tools.

This paper presents the routine implementation of a method for use of three-dimensional (3-D) treatment planning for breast cancer patients with node negative disease, treated with breast conserving surgery. The patients were positioned on a device which fitted a CT aperture with a diameter of 70 cm. A patient reference system was defined by the mamillary plane and the sternum midline. Eight to twelve CT images per patient were taken. The target volume was defined in several CT slices. The treatment planning was made with a 3-D treatment planning system; the treatment technique was isocentric with tangential fields. The patient position was the same at the CT scanner and during the treatment. Four to six portal films per field per patient were routinely taken. The reproducibility of the set-up was investigated on 20 consecutive patients: the treatment-to-treatment variation results were related to the margin of the target. The comparison between treatment planning and portal films gave information about the isocenter displacement. No large discrepancy between measurements on simulator film and on portal films was found. Based on the presented results the described treatment technique has been introduced as part of a routine clinical practice at our institution.     

Long-term clinical outcomes of postoperative pelvic radiotherapy with or without prophylactic paraaortic irradiation for stage I-II cervical carcinoma with positive lymph nodes: retrospective analysis of predictive variables regarding survival and failure patterns

We performed retrospective analysis to classify the risk hazard of patients with stage I-II cervical cancer with lymph node metastases treated with postoperative radiotherapy. From 1981 to 1995, 106 patients with early stage cervical carcinoma who received adjuvant pelvic radiation were entered in the analysis. The median patient age was 53.0 years (range 21-73). The median dose of 45.3 Gy (range, 32.1-56.4 Gy) was delivered over the whole pelvis. Seventy patients also received prophylactic paraaortic radiation (median 44 Gy; range 22-46 Gy). The 5/10-year overall survival (OAS), disease-free survival (DFS), pelvic control, and distant metastasis-free survival rates were 69.1/63.5%, 62.4/58.1%, 85.7/84.3%, and 74.1/71.6%, respectively. In the uni-/multivariate analyses, the significant prognostic factors of OAS and DFS proved to be disease stage, duration period between operation and radiotherapy, histology, and presence or absence of common iliac lymph node metastasis. Using the results of these analyses, we devised a predictive model for DFS. In this model, the 5-year DFS rates of patients with low (N = 35), intermediate (N = 59), and high-risk factors (N = 12) were 88.1%, 56.7%, and 16.7%, respectively (p < 0.0001). The majority of analyzed patients did not have adequate DFS estimates in this series. High-risk patients should receive a more intensive strategy, such as concurrent chemoradiotherapy. On the other hand, the effort to reduce toxicity should be considered carefully.     

子宫颈癌患者血清、盆腔淋巴结HPV检测及其相关性探讨

目的:检测宫颈癌患者原发灶、血清及其盆腔淋巴结中HPV DNA及亚型,探讨其相关性及临床意义。方法:选取16例行广泛全子宫切除术和盆腔淋巴结清扫术宫颈癌患者的原发灶组织、术前静脉血与盆腔淋巴结石蜡组织,运用PCR方法对上述标本进行HPV DNA及亚型的检测。结果:宫颈癌原发灶组织、血清标本中HPV DNA阳性率为50%(8/16)。16例盆腔淋巴结石蜡组织中13例为HPV DNA阳性(13/16,81.25%),其中总共切除的133个淋巴结中60个为阳性(60/133,45.1%),8例淋巴结HPV DNA阳性的病例其对应的原发灶组织也为阳性且两者亚型相同。盆腔淋巴结中的HPV DNA阳性率为45.1%(60/133),显著高于病理证实的淋巴结转移率1.5%(2/133)。6例患者(6/16,37.5%)原发灶、血清、盆腔淋巴结同时均为HPV DNA阳性;2例患者(2/16,12.5%)原发灶、盆腔淋巴结中HPV DNA表达阳性,而血清为阴性;1例患者(1/16,6.25%)淋巴结、血清HPV DNA阳性,而原发灶为阴性;未发现原发灶、血清HPV DNA表达阳性而淋巴结为阴性的病例,而且以上HPV DNA阳性的病例同一个患者对应的HPV亚型也相同。结论:宫颈癌患者血清中HPV DNA检出率与临床分期无关。宫颈癌患者盆腔淋巴结的HPV DNA检测可提高病理诊断淋巴结转移的阳性率,并且淋巴结中HPV DNA的检出率与原发灶的分化程度相关。宫颈癌原发灶、血清、盆腔淋巴结中HPV感染可能存在相关性。     

The impact of patient positioning on the adequate coverage of the uterus in the primary irradiation of cervical carcinoma: a prospective analysis using magnetic resonance imaging.

BACKGROUND AND PURPOSE: The intention of this prospective study is to assess the influence of different patient positionings and the use of belly boards on the coverage of the uterus by standard radiation fields. MATERIAL AND METHODS: In 21 women with carcinoma of the uterine cervix magnetic resonance imaging (MRI) scans in prone patient position with and without belly board and computed tomography (CT) scans in supine position were analysed after superimposing standard pelvic box fields. Further, all patients underwent a second MRI field control in prone position with belly board to detect intraindividual variations in the uterus position during treatment. RESULTS: Standard portals did not completely cover the uterus in supine position in 7/21 (33%), in prone position with belly board in 7/21 (33%) and without belly board in 5/21 (24%). Insufficient uterine coverage was found only in the anteroposterior direction. The mean distance (+/- standard deviation) between the field borders of the lateral portals and the uterus was in supine position anteriorly 3.4 cm (+/-2.2 cm) and posteriorly 1.8 cm (+/-1.3 cm), in prone position with belly board anteriorly 2.2 cm (+/-2.7 cm) and posteriorly 2.6 cm (+/-1.6 cm), prone without belly board anteriorly 3.3 cm (+/-2.4 cm) and posteriorly 1.9 cm (+/-1.1 cm). The difference was statistically significant between supine and prone position with belly board and between prone position with and without belly board. Repeated MRI controls during therapy showed no significant changes compared to the MRIs at the beginning of therapy. CONCLUSIONS: The use of standard radiation fields results in a high percentage of geographical misfits. Three-dimensional treatment planning is a prerequisite for adequate uterus coverage.     

Expression of CD3-zeta on T-cells in primary cervical carcinoma and in metastasis-positive and -negative pelvic lymph nodes

Lymphocytic infiltrate is often present in cervical cancer lesions, possibly reflecting an ongoing, but ineffective, immune response to the tumour. Recently, evidence has accumulated for systemically impaired T-cell functions in cancer patients, associated with decreased expression of signal-transducing zeta (zeta) chain dimer molecules on circulating T-cells and NK-cells. Here, we report on the intralesional down-regulation of zeta chain expression on T-cells in cervical carcinoma. Paraffin-embedded or snap-frozen sections from 24 different cervical cancer specimens were studied. Paraffin-embedded tumour-positive (n = 7) and tumour-negative (n = 15) pelvic lymph nodes were also included in the study. Immunostaining was performed on consecutive sections with antibodies specific for CD3-epsilon or the CD3-associated zeta chain dimer. Antigen retrieval by sodium citrate/microwave treatment was essential for zeta staining of paraffin sections. The amount of zeta positive cells was quantitated and related to the number of CD3-epsilon+ cells in corresponding tumour areas. Of the 24 cervical cancer specimens studied, zeta chain dimer expression was reduced in seven cases and strongly reduced in the other 17 samples. In tonsil control sections, CD3-epsilon and CD3-zeta were always co-expressed in almost equal numbers. Also, both tumour-negative and -positive lymph nodes showed zeta chain expression which equalled that of CD3-epsilon expression. These data indicate that a decreased expression of signal-transducing zeta molecules on tumour-infiltrating T-cells is frequent in cervical cancer. The apparently unimpaired zeta chain expression within draining lymph nodes suggests that local tumour-derived factors at the primary site are instrumental in zeta chain down-regulation.     

Radiation therapy for cutaneous squamous cell carcinoma involving the parotid area lymph nodes: dose and volume considerations

PURPOSE: The intraparotid and periparotid lymph nodes are the most commonly involved when skin cancer of the head and neck metastasizes beyond the primary site. We sought to report the clinical outcome of patients treated with radiation therapy for parotid-area metastases from cutaneous squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: The records of 36 patients treated with radiation therapy for cutaneous squamous cell carcinoma involving the parotid-area lymph nodes were reviewed. All patients had clinically N0 necks and were without evidence of distant disease. Thirty patients (83%) were treated postoperatively after gross total tumor resection. Median dose to the parotid area was 60 Gy (range, 50-72 Gy). Treatment of clinically N0 necks consisted of surgical dissection (7 patients), irradiation (15 patients), and observation (14 patients). RESULTS: The 5-year estimate of local (parotid) control was 86% in patients treated using surgery with postoperative therapy and 47% in patients treated using radiation therapy alone. Three of 4 patients with tumors that relapsed locally after surgery and postoperative radiation received a dose of less than 60 Gy. Elective neck irradiation decreased the incidence of subsequent nodal failures from 50% to 0% and significantly improved neck control (p < 0.001). The 5-year overall survival rate was 63%. CONCLUSIONS: Surgery followed by radiation therapy to doses of at least 60 Gy results in effective local control for patients with parotid area metastasis from cutaneous squamous cell carcinoma. Routine irradiation of the clinically N0 neck is recommended.     

Ectopic decidual cell reaction in para-aortic and pelvic lymph nodes in the presence of cervical squamous cell carcinoma during pregnancy

Bilateral para-aortic lymphadenectomy is routine prior to radical surgery in cancer of the cervix. A pregnant patient with invasive cancer of the cervix and ectopic decidual cell reaction in para-aortic and pelvic nodes is presented. A decidual cell reaction in frozen sections of para-aortic lymph nodes could be confused with metastatic disease. Pathogenesis of ectopic decidual cell reaction is discussed.     

The number of pelvic lymph nodes in the quality control and prognosis of radical hysterectomy for the treatment of cervical cancer.

AIMS: To determine if the number of removed lymph nodes in radical hysterectomy with lymphadenectomy (RHL) influences survival of patients with early stage cervical cancer and to analyze the relation of different factors like patient age, tumour size and infiltration depth with the number of nodes examined in node-negative early stage cervical cancer patients. METHODS: Of consecutive patients, who underwent RHL between January 1984 and April 2005, 331 had negative nodes (group A) without adjuvant therapy and 136 had positive nodes (group B). The Kaplan-Meier method and Cox regression model were used to detect statistical significance. Factors associated with excision of nodes were confirmed with linear regression models. RESULTS: The median number of removed nodes was 19 and 18 for group A and group B, respectively. There was no significant relationship between the number of removed nodes and the cancer specific survival (CSS) or disease free survival (DSF) for patients of group A (p=0.625 and p=0.877, respectively). The number of removed nodes in group B was not significantly associated with the CSS (p=0.084) but it was for the DSF (p=0.014). Factors like patient age, tumour size and infiltration depth were not associated with the number of nodes. CONCLUSIONS: No relation was found between the number of negative nodes examined after RHL for the treatment of early stage cervical cancer and CSS or DFS. However, a higher amount of removed lymph nodes leaded to a better DFS for patients with positive nodes. It is suggested that patients with positive nodes benefit from a complete pelvic lymphadenectomy and a sufficient yield of removed nodes.     

Route from the paraaortic lymphatic system to the tracheobronchial lymph nodes evidenced on lymphangiogram in a patient with gastric cancer

Lung metastasis from gastric or colonic cancer, without liver metastasis, is seldom seen. However, its metastatic pathway has not been delineated on imaging. We present and discuss such a lymphatic route in a patient with gastric cancer. The appearance of the mediastinum on a lymphangiogram is discussed. To the best of our knowledge, the lymphangiographic demonstration of the route from the paraaortic lymphatics to the tracheobronchial lymph nodes has been not reported. Lymphatics running from the paraaortic to the tracheobronchial lymph nodes through the diaphragm may play an important part in direct metastasizing to lung or tracheobronchial lymph nodes in certain patients.     

83例鼻咽癌放射治疗后颈淋巴结转移复发的治疗

目的 探讨颈淋巴结清扫术治疗鼻咽癌放射治疗后颈部淋巴结转移未控或复发患者的疗效。方法 回顾性分析因鼻咽癌放射治疗后颈淋巴结转移未控或复发行颈清扫术的83例患者，其中rN1期54例，rN2期19例，rN3期10例。按年龄、性别、放射治疗结束至手术之日的间隔时间、rN分期、是否行术后放射治疗、是否有软组织侵犯、病理检测阳性淋巴结个数和各组淋巴结阳性情况分为2个组。生存率分析采用Kaplan—Meier法，差异显著性检验采用Logrank法，多因素分析采用Cox模型。结果 1、3、5年总生存率分别为80、7％、47、1％、34．9％，其预后因素与有无软组织侵犯、放射治疗结束至手术之日间隔时间有关，术后放射治疗可提高生存率。结论 鼻咽癌放射治疗后颈部复发或未控的淋巴结的治疗可采用根治性颈淋巴结清扫术，对有包膜浸润和(或)周围软组织侵犯的患者可补充放射治疗。     

子宫颈癌患者血清、盆腔淋巴结HPV检测及其相关性探讨

目的：检测宫颈癌患者原发灶、血清及其盆腔淋巴结中HPVDNA及亚型,探讨其相关性及临床意义。方法：选取16例行广泛全子宫切除术和盆腔淋巴结清扫术宫颈癌患者的原发灶组织、术前静脉血与盆腔淋巴结石蜡组织,运用PCR方法对上述标本进行HPVDNA及亚型的检测。结果：宫颈癌原发灶组织、血清标本中HPVDNA阳性率为50％（8／16）。16例盆腔淋巴结石蜡组织中13例为HPVDNA阳性（13／16,81．25％）,其中总共切除的133个淋巴结中60个为阳性（60／133,45．1％）,8例淋巴结HPVDNA阳性的病例其对应的原发灶组织也为阳性且两者亚型相同。盆腔淋巴结中的HPVDNA阳性率为45．1％（60／133）,显著高于病理证实的淋巴结转移率1．5％（2／133）。6例患者（6／16,37．5％）原发灶、血清、盆腔淋巴结同时均为HPVDNA阳性;2例患者（2／16,12．5％）原发灶、盆腔淋巴结中HPVDNA表达阳性,而血清为阴性;1例患者（1／16,6．25％）淋巴结、血清HPVDNA阳性,而原发灶为阴性;未发现原发灶、血清HPVDNA表达阳性而淋巴结为阴性的病例,而且以上HPVDNA阳性的病例同一个患者对应的HPV亚型也相同。结论：宫颈癌患者血清中HPVDNA检出率与临床分期无关。宫颈癌患者盆腔淋巴结的HPVDNA检测可提高病理诊断淋巴结转移的阳性率,并且淋巴结中HPVDNA的检出率与原发灶的分化程度相关。宫颈癌原发灶、血清、盆腔淋巴结中HPV感染可能存在相关性。     

热疗配合化疗治疗鼻咽癌颈部淋巴结转移的临床观察

目的 初步探讨热疗配合化疗(热化疗)治疗鼻咽癌颈部淋巴结转移患者的近期疗效. 方法选择我科收治的中晚期鼻咽癌并颈淋巴结转移患者36例,按患者入院先后次序以及有否热疗禁忌证随机分两组,治疗组20例给予2周期的热化疗,对照组16例予单纯化疗,观察两组患者的肿瘤转移灶的缓解率、生活质量等. 结果治疗组CR 9例,PR 10例,SD 1例;对照组CR 4例,PR 7例,SD 5例.结论 热化疗在鼻咽癌颈部淋巴结转移的辅助性化疗中应用简便且安全,有较好的近期疗效,能改善患者的生存质量.     

Immunohistochemical detection of occult metastases in paraaortic lymph nodes in advanced gastric cancer.

Some Japanese surgeons have examined the utility of super-extended paraaortic lymphadenectomy (PAL) as part of the surgical treatment for advanced gastric cancer. However, therapeutic value of this PAL remains controvertial. The purpose of this study was to evaluate appropriate candidates who might benefit from PAL by the immunostaining with cytokeratin (CK) of the macroscopically intact paraaortic nodes. A total of 525 paraaortic nodes from 35 patients was serially sectioned and stained with hematoxylin-eosin (H&E) and CK staining. A total of 17 nodes (3.2%) from 7 patients (20.0%), among 525 macroscopically intact paraaortic nodes, was determined to be immunopositive for CK. In 4 patients, 8 H&E-positive nodes with metastases were all immunopositive and, in addition, 4 H&E-negative nodes were also immunopositive. Furthermore, 3 patients with H&E-negative nodes had five immunopositive nodes. Immunostaining with CK was useful for detection of occult metastases. Survival was prolonged in 3 of these 7 patients. The incidence of CK-positive nodes was significantly higher in patients with gross type of 3 or 4 gastric cancer and in patients with H&E-detected nodal metastasis within group 3 (N3) nodes. It seems that such patients would benefit from prophylactic PAL.     

Intensity-modulated radiotherapy for the treatment of pelvic lymph nodes in prostate cancer

Evaluation of: Wang-Chesebro A, Xia P, Coleman J, Akazawa C, Roach M 3rd: Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with 3D conformal radiation therapy in clinically localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 66, 654-662 (2006). A large randomized Phase III trial (RTOG 94-13) demonstrated improved progression-free survival for the irradiation of the pelvic lymphatics compared with treatment of the prostate only in patients with a high risk of lymph node involvement. Recent studies have indicated that the conventional target volume might miss substantial parts of the lymphatic drainage of the prostate. This retrospective planning study compared conventional, 3D-conformal and intensity-modulated radiotherapy (IMRT) for the treatment of pelvic lymph nodes. Field-shaping based on bony landmarks was shown to result in inadequate target coverage compared with 3D-conformal and IMRT planning. Regarding sparing of rectum, bladder, small bowl and penile bulb, the IMRT plans were highly superior. In summary, IMRT may result in increased rates of regional control with simultaneously decreased rates of toxicity. Integration of functional imaging into treatment planning and image guidance during treatment is expected to further improve the therapeutic ratio.