Ultrastructural effects of irradiation on squamous cell carcinoma of the head and neck

Tissue samples taken before and during the radical irradiation of the squamous cell carcinoma of the head and neck region were studied by light and electron microscopic examination. Radiation-induced cellular changes of which nuclear atypia was most pronounced. The tumor invasion pattern remained unchanged but the number of mitoses decreased. The lymphocytic infiltration increased at the beginning of the therapy (from 10-30 Gy) but decreased at the end of radiotherapy. The amount of neutrofils and the keratinization pattern remained almost unchanged at the light microscopic level, but intracellular filaments and desmosomes slightly increased in electron microscopic study. The changes in nuclear morphologic features pointing in a more undifferentiated direction are considered to be due to cell damage rather than to the more aggressive behavior of the tumor cells. This is in agreement with the decrease of mitoses which is due to radiation-induced arrest of tumor cells to the G2 phase. These changes might be related to the disappearance of tumors during irradiation. The leukocyte compartment seen in the samples might take part in the destruction of the tumor cells and in the removal of the cell debris.     

低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤中的价值

背景与目的：颅内生殖细胞肿瘤（intracranial germ cell tumors）经积极放化疗常可获得令人满意的局部控制率和生存率，然而对部分无法取得病理诊断的颅内生殖细胞肿瘤的治疗，研究者们至今无法达成一致意见。该研究探讨低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤的可行性及临床意义。方法：该研究分析了贵州省人民医院及北京天坛医院收治的28例（16例男性，12例女性，中位年龄14.5岁）高度怀疑为颅内生殖细胞肿瘤的患者。患者血浆和（或）脑脊液人绒毛膜促性腺激素（β-human chorionic gonadotropin，β-HCG）和甲胎蛋白（α-fetoprotein，AFP）均为阴性，头颅MRI诊断提示鞍区和（或）松果体区呈典型生殖细胞肿瘤影像特征，临床表现高度提示可能为生殖细胞瘤（germinoma）。这些患者因无法通过手术及立体定向活检明确病理诊断，或患者本身不同意手术或活检，因此我们建议实施诊断性低剂量放疗联合化疗方案，诊断性放疗剂量为3.4 Gy，1.7 Gy/2次。经低剂量诊断性放疗后行MRI复查。随后根据MRI复查结果采用以下治疗：⑴ 影像学为进展（progression disease，PD）或稳定（stable disease，SD），建议手术治疗。⑵ 影像学达完全缓解（complete response，CR）或部分缓解（partial release，PR），再予以2个周期化疗，顺铂+足叶乙甙（DDP+VP16）方案2个周期，化疗后再次行MRI复查，如果患者影像学检测结果显示达CR，随即按生殖细胞瘤进行调强放疗（intensity-modulated radiation therapy，IMRT）及三维适形放疗（three-dimensional conformal radiotherapy，3D-CRT)。放疗方案根据患者情况进行选择：① 局部放疗；② 全脑全脊髓+局部加量放疗；③ 全脑+局部加量放疗（松果体区病变总剂量小于等于50.4 Gy；鞍区病变总剂量小于等于41.0 Gy）。⑶ 经低剂量诊断性放疗联合化疗后行MRI复查，如果患者影像学仍未达CR，建议患者立即接受手术治疗。参考WHO实体瘤疗效评价标准判断放化疗效果。结果：经诊断性放疗后显示为SD的患者1例，被随后的手术证实为垂体瘤。经低剂量诊断性放化疗后，病灶影像学诊断结果显示26例达CR，考虑临床诊断为颅内生殖细胞肿瘤，随即予患者行IMRT及3D-CRT；治疗后影像学复查均为CR，以上患者随访时间1~8年，所有患者均无瘤生存，无复发，未见放射性坏死。经诊断性放疗及2个周期化疗后仍有1例患者影像学诊断结果显示未达到CR，后经手术证实为混合性生殖细胞肿瘤。结论：低剂量诊断性放疗联合化疗具备区分颅内生殖细胞瘤与非生殖细胞瘤的能力，对高度怀疑为颅内生殖细胞肿瘤的患者, 在没有病理证实的情况下，可参考此方案进行诊断性治疗和临床处理。     

Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer.

BACKGROUND AND PURPOSE: PET with (18)F-Misonidazole (FMISO-PET) is a non-invasive method for measuring tumor hypoxia. We analysed changes of FMISO-uptake during radiotherapy and their impact on patient outcome. MATERIALS AND METHODS: Fourteen patients with HNC underwent repeated FMISO-PET prior to radiotherapy and after 30Gy. Dynamic and static PET-scans (2+4h p.i.) were acquired. FMISO-uptake was quantified by calculating standard uptake values (SUV) and tumor-muscle-ratios (TMR). Kinetic curve types representing tissue hypoxia were defined. Change of curve type was correlated with patient outcome. RESULTS: The mean SUV 4h p.i. and the TMR decreased significantly during radiotherapy. SUV decreased clearly in 12/14 patients, and increased in 2 patients. TMR decreased in 11 patients, and increased in 3 patients. Prior to radiotherapy, three different shapes of kinetic curve types indicative for the degree of hypoxia could be defined in 12/14 patients: (1) accumulation type (severe hypoxia (n=8)), (2) intermediate type (intermediate degree of hypoxia (n=3)), and (3) wash-out type (low degree of hypoxia (n=1)). Curve type changed towards a lower degree of hypoxia at 30Gy in all but 3 patients. In three patients curve type remained unchanged. CONCLUSIONS: The changes in tumor FMISO-uptake during radiotherapy indicate radio-induced reoxygenation.     

Local low-dose interleukin-2 induces systemic immunity when combined with radiotherapy of cancer. A pre-clinical study

Tumor recurrence and outgrowth of metastases limit the therapeutical effect of radiotherapy. We have tested whether these problems can be overcome by supplementing radiotherapy with locoregional interleukin-2 (IL-2) treatment. The SL2 lymphoma and the M8013 mammary carcinoma were used. Mice bearing a 10-day-old s.c. tumor were locally irradiated and were treated daily with IL-2 peritumorally for 5 or 10 days. Low-dose IL-2 therapy improved local response (LR) and increased disease-free survival (DFS) in both tumor models following either single-dose irradiation or fractionated irradiation. For example, 93% of SL2-bearing mice treated with single-dose irradiation and 10 days of IL-2 experienced long-term DFS, compared with 17% for irradiation alone (p < 0.0001). Additionally, treatment of one tumor with irradiation +IL-2 led to anti-tumor effects in a second, untreated tumor in 80% of SL2-bearing mice. LR was increased to 100% and DFS to 70% when the second, non-irradiated tumor was also treated with peritumoral IL-2. We conclude that supplementing local radiotherapy with low doses of IL-2 results in increased local tumor control and regression of distant, non-irradiated tumors. This type of radioimmunotherapy is a promising new approach for the clinic. Int. J. Cancer 72:1003–1007, 1997. © 1997 Wiley-Liss, Inc.     

Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

PURPOSE: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. METHODS AND MATERIALS: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. RESULTS: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. CONCLUSION: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.     

The link between local recurrence and distant metastases in human breast cancer

Purpose: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination.Methods and Materials: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients.Results: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year after initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type.Conclusions: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases’ emergence, and death, which shows that tumors with or without LR have similar biological characteristics.     

何杰金淋巴瘤95例临床病理分析

From 1961 through 1986, 95 cases of Hodgkin's disease were biopsied in our hospital. Sex distribution: male 70, female 25. Age incidence: 27% were under 20 years and 75% under 40. 93% of lesions had originated from the lymph nodes. Clinical stage: I 14, II 37, III 25 and IV 19 cases. 20 patients were treated by chemotherapy, 26 by radiotherapy and 49 by combined chemotherapy and radiotherapy. The CR + PR rate was 86.2% and the 1-, 3-, 5- and 10-year survival rates were 83.2% (79/95), 57.6% (53/92), 46.4% (32/69) and 31.3% (15/48), respectively. The results showed that the 4 pathological types (LP, NS, MC, LD) and 10 subtypes (D,N in LP; LP, MC, LD in NS; LP, MC, LD in MC; R, DF in LD) and the predominance of reticulum cells (S-R cells, HD cells, histiocytes, lymphocytes, fibrosis, collagenous changes) in the tumor were all irrelevant to the prognosis (P greater than 0.05). However, the clinical stage, immediate response and the method of treatment were very prognostic (P less than 0.05) The authors believe that intensive chemotherapy combined with radiotherapy and intensive radiotherapy could lead to long survival.     

Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx.

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.     

Predictive factors of local-regional recurrences following parotid sparing intensity modulated or 3D conformal radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Predictive factors for local-regional (LR) failures after parotid-sparing, Intensity modulated (IMRT) or 3D conformal radiotherapy for head and neck (HN) cancers were assessed. PATIENTS AND METHODS: One hundred and fifty-eight patients with mostly stages III-IV HN squamous cell carcinoma underwent curative bilateral neck irradiation aimed at sparing the parotid glands. Patient, tumor, and treatment factors were analyzed as predictive factors for LR failure. RESULTS: Twenty-three patients had LR recurrence (19 in-field and four marginal). No differences were found in the doses delivered to the PTVs of patients with or without in-field recurrences. In univariate analysis, tumor site was highly predictive for LR failure in both postoperative and definitive RT patients. In postoperative RT patients, pathologic tumor size, margin status, extracapsular extension (ECE) and number of lymph node metastases, were also significantly predictive. Multivariate analysis showed tumor site (oropharynx vs. other sites) to be a significant predictor in all patients, and involved margins and number of involved lymph nodes in postoperative patients. CONCLUSIONS: Clinical rather than dosimetric factors predicted for LR failures in this series, and were similar to those reported following standard RT. These factors may aid in the selection of patients for studies of treatment intensification using IMRT.     

Metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck.

68 patients with metastatic squamous-cell carcinoma (SCC) of an unknown primary tumor localized to the neck were treated between 1981 and 1990. There were 11 patients treated with radiotherapy alone, 24 patients treated with surgery and radiotherapy and 33 patients treated with radiotherapy and chemotherapy. Male to female ratio was 1.9:1 and the median age was 55 years (range, 33 to 71 years). 41 (61%) patients had N3 disease, 18 (26%) patients had N2 disease and 9 (13%) patients had N1 disease. The majority of N3 patients were treated with radiotherapy + chemotherapy (n = 17) and surgery + radiotherapy (n = 17). The complete response (CR) to radiotherapy + chemotherapy was 73% with 19 patients having no evidence of disease currently. The median survival time (MST of this group was 34+ months. Of the 35 patients who had surgery and/or radiotherapy, 7 (20%) currently have no evident disease. The MST of these two groups (combined) was 22 months. Patients with N3 disease who received radiotherapy + chemotherapy had a higher CR rate and longer MST when compared with those without chemotherapy.     

血清肿瘤标志物对晚期原发性肺癌老年患者放疗疗效的评估价值

目的：探讨血清肿瘤标志物对晚期原发性肺癌老年患者放疗疗效的评估价值。方法纳入156例晚期原发性肺癌老年患者,放疗结束6周后比较患者的近期疗效并将患者分为完全缓解（complete response, CR）+部分缓解（partial response,PR）组（即CR+PR组）、疾病稳定（stable disease,SD）组（即SD组）及疾病进展（progressive disease,PD）组（即PD组）,比较不同组患者治疗前后血清中癌胚抗原（carcinoembryonic antigen, CEA）、细胞角蛋白21-1片段（human cytokeratin fragment antigen 21-1,CYFRA21-1）、鳞状细胞癌抗原（squa-mous cell carcinoma,SCC）及癌抗原125（carbohydrate antigen 125,CA125）的水平,并计算以血清肿瘤标志物水平评估放疗疗效的方法的灵敏度和特异度。结果156例患者放疗后,CR有2例（1.28%）,PR有83例（53.21%）,SD有22例（14.10%）,以及PD有49例（31.41%）。放疗后CR+PR组患者的CEA、CYFRA21-1、SCC及CA125水平均显著低于治疗前水平（P＜0.05）,SD组患者治疗后各血清肿瘤标志物水平与治疗前无明显差异（P＞0.05）,PD组患者治疗后各血清肿瘤标志物水平均显著高于放疗前水平（P＜0.05）。以血清肿瘤标志物水平评估放疗疗效的方法的灵敏度为72.94%,特异度为76.06%。结论血清肿瘤标志物CEA、CYFRA21-1、SCC及CA125可较准确地评估晚期原发性肺癌老年患者的放疗疗效,并具有较高的灵敏度与准确度。     

Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a Report by the Radiation Therapy Oncology Group

Since February 1981, 300 patients with superficial measurable tumors were randomized on an RTOG protocol (81-04) involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (42.5 degrees C, 60 min). This is a report of 218 eligible patients with single lesions: 107 treated with radiotherapy alone (RT), 111 with radiotherapy plus hyperthermia (RT + HT). Only 56% of the 24 tumors less than 3 cm and 36% of the 53 lesions larger than 3 cm received what was felt to be "adequate" therapy (greater than or equal to 29 Gy and 8 heating sessions). Overall complete response (CR) was observed in 28% of the patients treated with RT, and 32% of the patients receiving RT and heat. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In the head and neck tumors less than 3 cm in diameter there was no difference in CR with irradiation alone or combined with hyperthermia (46% vs 43%). However, in the breast, and trunk and extremities a better CR rate was noted with irradiation and heat (55% and 67%) than with irradiation alone (33% and 0). In lesions less than 3 cm treated with irradiation and heat the probability of remaining in response was 80% compared with 15% with irradiation alone. In lesions larger than 3 cm no difference in CR was observed in either treatment group. It has been hypothesized that the response rate is higher in patients with smaller lesions (less than 3 cm) and in breast/chest wall, trunk/extremity lesions because these tumors and anatomical sites are easier to heat adequately. Problems encountered in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to accurately represent the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because of short survival of some patients and occasionally rapid tumor regression that may cause necrosis which may be misinterpreted as persistent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)     

Factors influencing complete response and survival in patients with head and neck cancer treated with platinum-based induction chemotherapy. A Hellenic Co-operative Oncology Group Study.

One hundred fifteen consecutive patients with locally advanced carcinoma of the head and neck were treated between August 1984 and August 1989 with three cycles of either of two platinum-based induction chemotherapies, followed by local treatment. After the completion of chemotherapy 26 (23%) patients had complete responses (CR). Several pre-treatment characteristics were analyzed for a possible correlation to CR to induction chemotherapy and to survival. The following variables were closely interrelated: sex, history of smoking, alcohol abuse, histologic type, tumor site and grade. Tumor stage and negative history of smoking were correlated with CR. The variables which were individually correlated with survival were keratinization, CR to chemotherapy, alcohol abuse, histologic type, site and grade of the primary tumor, serum albumin level and tumor stage. A regression analysis after Cox's model to identify a limited set of predictors selected CR, serum albumin, tumor grade, performance status and nodal status as the most significant; when analyzing the data without the time-dependent variable CR, the factors selected by the model were serum albumin, tumor grade, performance status and tumor stage. In conclusion, serum albumin level, tumor grade, performance status and tumor stage prior to treatment can be used to define risk classes in our patient population.     

The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma

Tumor perineural dissemination is a hallmark of human pancreatic ductal adenocarcinoma (PDAC) and represents a major source of local tumor recurrence after surgery. In this study, we provide in vitro and in vivo evidence that the chemokine receptor CX3CR1 may be involved in the neurotropism of PDAC cells to local peripheral nerves. Neoplastic cells from PDAC cell lines and surgical specimens express the chemokine receptor CX3CR1, absent in normal pancreatic ducts. Its unique ligand, the transmembrane chemokine CX3CL1, is expressed by neurons and nerve fibers. CX3CR1 + PDAC cell lines migrated in response to human recombinant CX3CL1 and specifically adhered to CX3CL1-expressing cells of neural origin via mechanisms involving activation of G proteins, beta1 integrins, and focal adhesion kinase. In vivo experiments with transplanted PDAC showed that only CX3CR1-transfected tumor cells infiltrated the local peripheral nerves. Immunohistochemistry of CX3CR1 in PDAC specimens revealed that 90% of the samples were positive with a heterogeneous pattern of expression. High receptor score was significantly associated with more prominent tumor perineural infiltration evaluated histologically (P = 0.026). Regression analyses (univariate and multivariate) showed that high CX3CR1 expression and perineural invasion were strongly associated with local and earlier tumor recurrence (P = 0.007). Collectively, this study shows that the CX3CR1 receptor may be involved in PDAC tumor neurotropism and is a relevant and independent risk factor to predict an early local tumor relapse in resected patients. Thus, the CX3CR1-CX3CL1 axis could represent a valuable therapeutic target to prevent tumor perineural dissemination in pancreatic cancer.     

Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17

One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life-threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck.     

Two distinct local relapse subtypes in invasive breast cancer: effect on their prognostic impact.

PURPOSE: Local relapse (LR) remains an important concern in breast cancer surveillance. Given the unique opportunity to study local recurrences in the breast in the absence of irradiation, we tested the possibility of identifying a particular tumor feature that might account for LR. EXPERIMENTAL DESIGN: Archival specimens from 235 patients belonging to the control arm (no radiotherapy) of the Milan 3 Trial were retrieved and included in this study. H&E-stained histologic slides were reviewed for diagnostic reassessment. A panel of biological variables was assessed by immunohistochemical/cytochemical staining. RESULTS: Onset of LR was significantly linked only to patient's age, with a hazard ratio (HR) to relapse reduced by 60% in patients >50 years of age (P = 0.002). Univariate and multivariate Cox analyses in women 50 years of age, lymph node and estrogen receptor status were significantly predictive of LR (HR, 3.34; P = 0.0113 and HR, 0.39; P = 0.0424, respectively). Multivariate analysis indicated that apart from lymph node positivity (HR, 3.48; P = 0.0120), none of the variables associated with LR in univariate analysis displayed an independent LR-predictive power. LR had a strong prognostic impact on distant metastasis in patients >50 years of age, whereas in younger women, LR did not affect the risk of metastasis. CONCLUSIONS: These results support the notion that LR arises from two distinct mechanisms, one that is more frequent in young patients, associated with host characteristics, and is not linked with prognosis, and another that is less frequent, but is associated with tumor aggressiveness which represents a peculiar and distinct marker of breast tumor malignancy.     

临床无转移食管鳞癌肿瘤局部因素对治疗失败模式的影响

目的 分析临床无转移食管鳞癌(ESCC)患者肿瘤局部因素对区域性复发和远处转移的影响。方法 对 236例符合入组条件的ESCC患者进行回顾性分析,主要分析食管造影病变长度、肿瘤最大横径及肿瘤体积对患者生存及治疗失败模式的影响。Kaplan-Meier法计算OS等,Cox模型多因素分析。结果 全组患者1、3、5年OS率,复发率及远处转移率分别为88.6%、52.4%、30.2%,15.5%、35.6%、45.8%及9.0%、22.2%、30.6%。多因素分析结果显示近期疗效、肿瘤最大横径为患者OS率的影响因素(P=0.000、0.019);性别、肿瘤最大横径、照射方式、近期疗效为患者复发的影响因素(P=0.039、0.003、0.045、0.000);肿瘤最大横径为患者远处转移的影响因素(P=0.035)。肿瘤最大横径为ENI及IFI组患者复发的影响因素(P=0.008、0.001);病变造影长度、肿瘤最大横径、肿瘤体积为ENI组患者远处转移的影响因素(P=0.009、0.023、0.014)。结论 临床无转移ESCC患者肿瘤局部因素对区域性复发和远处转移均有显著影响,其中肿瘤最大横径尤为重要。     

基于放疗中重复四维CT的食管癌大体肿瘤体积与位移的相关性

目的 基于放疗中重复4DCT增强扫描探讨胸段食管癌原发肿瘤分次放疗内大体肿瘤体积大小、长度及最大橫径与位移的相关性。方法 32例胸段食管癌患者分别于放疗前及10、20、30次时行4DCT模拟定位增强扫描,获取各次4DCT扫描GTV三维方向位移并分析其与体积、长度及最大横径的相关性。结果 放疗20次时,全部患者、胸下段癌患者肿瘤体积与左右方向位移呈正相关(P=0.012、0.040),全部患者、胸上、中段癌患者肿瘤长度与GTV上下方向位移呈正相关(P=0.003、0.031、0.044),胸下段癌患者肿瘤长度与GTV左右方向位移呈正相关(P=0.027)。初次扫描全部患者最大橫径与GTV左右方向、上下方向、三维运动矢量均呈正相关(P=0.036、0.033、0.018),胸下段癌患者最大橫径仅与GTV左右方向位移相关(P=0.011)。结论 放疗中各时段各部位食管癌体积、长度及最大横径与GTV前后方向位移均无相关性,而在左右、上下方向的相关性则依病变部位及疗程时段不同而异。     

Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis.

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.     

番茄红素对荷卵巢癌大鼠免疫功能的影响及其机制研究

目的 研究番茄红素(LP)改善荷卵巢癌大鼠免疫功能的作用并探讨其机制。方法 将卵巢癌细胞NUTU-19接种于腋窝皮下,制备荷卵巢癌大鼠模型,取60只模型大鼠随机分为模型组、顺铂组(2 mg/kg)和LP(40、20、10 mg/kg)组,每组12只;各治疗组均隔天腹腔注射给药一次,共5次。观察各组大鼠一般生存状态和肿瘤生长状况;称量肿瘤重量并计算抑瘤率,通过HE染色观察肿瘤组织形态结构变化;噻唑蓝(MTT)比色法测定脾淋巴细胞转化率;酶联免疫(ELISA)法测定血清中白细胞介素-2(IL-2)和肿瘤坏死因子-α(TNF-α)含量;流式细胞仪术(Flow cytometry)检测血中T淋巴细胞亚群(CD4⁺、CD8⁺)百分率并计算CD4⁺/CD8⁺。结果 与模型组比较,发现LP各组大鼠饮食状况好转,瘤体减小、活动度和硬度较差,肿瘤组织细胞皱缩、呈片状坏死等病变,上述改变以LP 40 mg/kg组最为显著;LP(40、20 mg/kg)组瘤重显著减轻且抑瘤率显著升高(P＜0.05,P＜0.01),脾淋巴细胞转化率显著升高(P＜0.05,P＜0.01),血清中IL-2和TNF-α含量均显著降低(P＜0.05,P＜0.01),血液中CD8⁺百分率显著降低(P＜0.05,P＜0.01),LP 40 mg/kg组CD4⁺百分率显著升高(P＜0.05),LP(40、20 mg/kg)组CD4⁺/CD8⁺显著升高(P＜0.05,P＜0.01)。结论 LP具有提高荷卵巢癌大鼠免疫功能的作用,其机制可能与LP能够有效降低炎症细胞因子(IL-2、TNF-α)含量以及提高CD4⁺/CD8⁺比值有关。