Prediction of response to primary chemotherapy for operable breast cancer

The use of primary systemic cytotoxics leads to a high remission rate in patients with breast cancer. Response was identified as an important variable associated with survival. Thus, features which predict response, are potentially relevant for planning treatments and improving survival. Retrospectively, we investigated several histopathological features (expression of oestrogen and progesterone receptors, Mib1, bcl-2, c-erbB-2, and p53) prior to two programmes of either sequential preoperative chemotherapy (doxorubicin plus cyclophosphamide) and radiotherapy (Group A), or preoperative chemotherapy (5-fluorouracil, folinic acid and vinorelbine) alone (Group B) in patients with operable breast cancer. After three courses, patients with a partial or complete response were given a further three courses, which was followed for patients in Group A by radiotherapy 50 Gy plus a boost of 10 Gy. All patients were submitted to surgery after completion of preoperative treatment and pathology material from 73 patients (median age, 49 years, range, 30–70; performance status, 0–1; 68 T₂, 5 T₃) was obtained. The overall response rate according to radiological and clinical evaluation was 59% (68% for Group A and 49% for Group B). 12 of 14 patients with p53-positive tumours and 31 of 59 with p53-negative tumours responded (P=0.04). 6 of 7 patients with elevated c-erbB-2 had a response compared with 37 of 66 patients in the group with c-erbB-2 negative tumours (P=0.03). Mib1 expression decreased substantially (≥50%) in 25 patients during treatment, of whom 20 responded compared with 21 of 48 patients with a lower decrease (P=0.04). Response was observed in 28 of 37 patients with high baseline Mib1 (>20%) and in 15 of 36 patients in the low Mib1 group (P=0.05). Finally, 32 of 44 tumours with low expression of progesterone receptors responded compared with 11 of 29 tumours with high receptors expression (P=0.05). These markers might be useful for tailoring primary and postsurgical systemic treatments.     

Evaluation of chemotherapy of unresectable non-small cell lung cancer]

For this evaluation, a comparison was made of survival of 34 patients with non-small cell lung cancer who had undergone chemotherapy (Group B) with that of 38 patients without this chemotherapy (Group A). Group B had received neither radiotherapy for primary lesions nor bronchial artery infusion of anticancer drugs, and the chemotherapeutic regimen was CDDP + VDS or CDDP + VDS + MMC chemotherapy. MST of this group was significantly longer than that of Group A (4.5 months vs 7.3 months. P less than 0.01), but the PS features of the two groups differed significantly. A comparison was thus made of survival for PS 1-2 cases in both groups (Group A: 17 cases, Group B: 27 cases). MST of group A and B were 6.8 and 9.8 months, respectively (P less than 0.05). The efficacy of the treatment for prolonging survival in terms of age, sex, PS, histology, T factor, N factor and M factor was evaluated by multivariate analysis using the proportional hazard model of Cox. The results obtained indicated the chemotherapy significantly prolonged survival.     

喉鳞癌原发灶和切缘p53蛋白表达及其与术后放疗的关系

目的 分析喉鳞癌原发灶和病理学阴性切缘中p53蛋白表达与术后放疗的关系。方法 回顾性分析67例喉鳞癌的临床资料,采用免疫组化方法检测病理学阴性切缘和原发灶中p53蛋白表达情况。结果 切缘和原发灶中p53阳性率分别为19．4％(13／67)和50．7％(34／67)。在原发灶p53阳性组中,与术后未放疗者相比,术后放疗者的生存率较未放疗者高(P=0．0005),复发率比较低(P=0．002);而在原发灶p53阴性组中,术后放疗者的生存率、复发率与未放疗者差异无显著性(P=0．4096,P=0．175)。在切缘p53蛋白阳性组中,术后放疗者的生存率和复发率与未放疗者差异无显著性、(P=0．378l,P=1．0);在切缘p53蛋白阴性组中,术后放疗者的生存率和复发率与未放疗者差异无显著性(P=0．0743,P=0．248)。结论 对喉鳞癌原发灶p53蛋白阳性表达者进行术后放疗是有必要的,但病理学阴性、而p53蛋白阳性切缘暂不能作为术后放疗与否的依据。     

Arterial infusion chemotherapy for liver metastases from colorectal cancer--therapeutic effects of different protocols

The therapeutic effects of different protocols for arterial infusion chemotherapy were compared in patients with multiple liver metastases from colorectal cancer. A total of 49 patients with colorectal multiple liver metastases treated in our hospital since 1988 were the subjects. In order to compare the therapeutic effects on the regression of cancer and the survival rate, the subjects were assigned into Groups A-D, which were treated using different protocols. Group A received ADR, EPI, CDDP or 5-FU alone at first. If this drug was not effective, it was replaced with another of those mentioned here, and so on. Group B received CDDP 50 mg on day 1, 5-FU 500 mg/day from day 2 to day 7 and 5-FU 500 mg/day for 2 weeks thereafter (FP treatment). Group C received CDDP 50 mg at the time of reservoir insertion and 5-FU 1,000 mg for 5 hours thereafter (WHF treatment). Group D received 5-FU 1,000 mg for 24 hours on day 1, day 3, and day 5 of every week with combination of CDDP 5-10 mg/day from day 1 to day 5 and none on day 6 and day 7 (intermittent F + low-dose P treatment) for 3 weeks. The response rate was 33% for Group A (n = 18), 46% for Group B (n = 13), 25% for Group C (n = 8) and 80% for Group D (n = 10), showing significant differences between Group D and other groups. The 1-year survival rate was 50% for Group A, 46% for Group B, 29% for Group C and 89% for Group D. Significant differences in survival rate were found between Group B and D, and Group C and D.     

适形调强放疗联合化疗治疗中晚期非小细胞肺癌72例

目的:评价三维适形调强放疗联合化疗在治疗中、晚期非小细胞肺癌(NSCLC)的作用。方法:72例中、晚期NSCLC患者采用分组治疗。A组采用常规放疗加化疗,共30例;B组采用三维适形放疗加化疗,共30例;C组采用三维适形调强放疗加化疗,共12例。三组均采用铂类联合盖诺方案化疗1个周期后放疗,放疗结束后再化疗3~5个周期。结果:A组有效率(CR PR)43·3%,B组有效率70%·0,C组有效率83·3%,A组与B组,A组与C组差异有统计学意义,P<0·05;1年生存率:A组40·0%(8/20),B组为66·7%(12/18),C组为100·0%(4/4)。B、C组合并后的1年生存率与A组差异有统计学意义,P=0·03;三组的骨髓抑制等基本相同;放射性食管炎,三组间差异无统计学意义,P=0·16。急性放射性肺炎:A组56·7%,B组33·3%;C组16·7%。A组与C组差异有统计学意义,P=0·031。结论:在中、晚期NSCLC的治疗中,三维适形或调强放疗联合化疗与与常规放疗联合化疗相比,具有疗效好、毒副反应轻、患者容易耐受等特点;适形调强放疗在不增加放疗不良反应的同时,能够提高1年生存率和靶区的照射剂量。     

Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers

The predictive value of expression of p16INK4A, retinoblastoma (Rb) and p53 proteins for prognosis was evaluated in 76 patients with non-small-cell lung cancers (NSCLCs) that were potentially curatively resected between 1990 and 1995, using the results of immunostaining analyses of these proteins as reported in our previous study (Kinoshita et al, 1996). Of these NSCLCs, 22 (29%) lacked p16 protein expression and eight (11%) Rb protein, while 30 (39%) showed positive (altered) p53 protein expression. Survival of patients with p16-negative tumours was not significantly different from that of patients with p16-positive tumours (5-year survival rates 67% and 72% respectively, P = 0.8), nor was survival of patients with Rb-negative tumours significantly different from that of patients with Rb-positive tumours (5-year survival rates 42% and 69% respectively, P = 0.9). Moreover, survival of patients with p16/Rb-negative (either p16- or Rb-negative) tumours was not significantly different from that of patients with p16/Rb-positive (both p16- and Rb-positive) tumours (5-year survival rates 67% and 68% respectively, P = 0.7). In contrast, survival of patients with p53-positive (altered) tumours tended to be shorter than that of patients with p53-negative (unaltered) tumours (5-year survival rates 56% and 78% respectively, P = 0.06). In univariate analysis of potential prognostic factors, p16, Rb and p16/Rb proteins were not significant prognostic factors in the present cohort of potentially curatively resected NSCLCs. Altered p53 protein status tended to be a negative prognostic factor (P = 0.06 by the univariate analysis). These results indicate that loss of p16 protein alone, or in combination with loss of Rb protein, does not predict the clinical outcome of patients with resected NSCLCs.     

Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer

This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.     

Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.     

头颈鳞癌p53、Bcl-2及P-gp表达在治疗中的作用

目的 检测突变型p53、Bcl-2及P-gp蛋白在头颈鳞癌中的表达,探讨其在治疗中的作用.方法 97例头颈鳞癌中口咽癌18例、下咽癌27例、声门上喉癌52例,采用S-P法检测癌组织中p53、Bcl-2及P-gp蛋白表达,并结合治疗结果进行统计分析.结果 突变型p53、Bcl-2及P-gp蛋白在头颈鳞癌中的阳性表达率分别为69.07﹪、46.39﹪、50.52﹪.突变型p53蛋白阳性与阴性累计五年生存率分别为38.43﹪和75.86﹪.P-gP蛋白阳性与阴性分别为35.23﹪和63.15﹪,两者对比有统计学意义(P＜0.05).在单纯手术和术后放疗、化疗两组中,突变型p53蛋白阳性与阴性的五年生存率分别为40.77﹪和80.00﹪、25.63﹪和61.90﹪,对比均有统计学意义(P＜0.05).术后放疗、化疗组中Bcl-2和P-gp蛋白阳性与阴性的五年生存率分别为23.35﹪和48.83﹪、31.43﹪和60.53﹪,差别有统计学意义.结论 突变型p53、Bcl-2、P-gp蛋白阳性表达是抵抗放疗或化疗的生物学指标,在预测放疗、化疗敏感性方面有一定作用.     

P53 alteration and microsatellite instability have predictive value for survival benefit from chemotherapy in stage III colorectal carcinoma.

PURPOSE: We recently presented evidence for tumor site and gender-specificity in the survival benefit from adjuvant chemotherapy in Stage III colorectal cancer (CRC). In the current study, we examined whether p53 alteration or the microsatellite instability (MSI) phenotype provide additional predictive information in CRC patients. EXPERIMENTAL DESIGN: A retrospective series of 891 Stage III CRC patients with negative surgical margins was investigated. Thirty percent (270 of 891) received postoperative adjuvant chemotherapy with curative intent and comprising of 5-fluorouracil/levamisole. Adjuvant treatment and nontreatment patient groups were well matched for tumor site, grade, p53 alterations, and MSI. Surgical tumor specimens were investigated for p53 overexpression using immunohistochemistry and for p53 mutation and MSI using single-strand conformation polymorphism analysis. The predictive value of these markers was evaluated by comparing the survival of adjuvant-treated and nonadjuvant treated patients. RESULTS: A strong inverse correlation was observed between p53 alteration and MSI (P < 0.0001). In univariate analysis, the factors of sex, site, p53 alteration, and MSI were each strong predictors of a survival benefit from chemotherapy. Multivariate analysis revealed that chemotherapy provided maximal survival benefit for female patients (P = 0.005) and for patients whose tumors contained normal p53 (P = 0.041). Males whose tumors contained a p53 alteration and were negative for MSI appeared not to benefit from chemotherapy. CONCLUSIONS: Our findings suggest that p53 alteration and MSI could be clinically useful molecular predictive markers for the identification of CRC patients who might benefit from 5-fluorouracil-based chemotherapy.     

Induction chemotherapy for advanced head and neck cancer: modification of response to chemotherapy by antiemetics.

Forty Stage IV head and neck cancer patients were entered on a multimodality trial of induction chemotherapy (cisplatin + infusional 5-fluorouracil), surgery, and radiation. During chemotherapy, the patients of Group A (the first 19 patients) were medicated with metoclopramide. The patients of Group B (the next 21 patients) were medicated with droperidol. The groups were comparable. The response rate (complete + partial) was 32% for Group A and 52% for Group B (p = 0.16). Primary site (p = 0.08) and surgical margin (p = 0.005) clearance of tumor were better in Group B. Nodal disease responded poorly to chemotherapy in both groups. Tumor necrosis (p = 0.006) and granulation tissue (p = 0.07) were reduced in surgical specimens after chemotherapy in Group B. The drugs were well tolerated with reversible toxicity; nausea/vomiting (p = 0.01) and weight loss (p = 0.07) after chemotherapy, were increased in Group B. The 2-year survival was 26% for Group A and 62% for Group B (p = 0.027). The median survival was 15 months for Group A and 33 months for Group B (p = 0.05). Progression-free survival improved in Group B (p greater than 0.17). These improvements in response and survival did not appear to reflect changes in surgical or radiotherapy management, but may have reflected an uninhibited effect of cisplatin in Group B. It is theorized that the metabisulfite formulated with metoclopramide altered the pharmacokinetics or pharmacodynamics of cisplatin. This resulted in the poor response to chemotherapy and poor survival in Group A. An analysis of a randomized trial comparing metoclopramide (formulated with metabisulfite) versus a control antiemetic can confirm the data presented in this pilot study. Overall, our patients survived as well as others in comparable multimodality studies in Europe and the United States.     

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.     

Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02

BACKGROUND: The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men. PATIENTS AND METHODS: Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200). Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided. RESULTS: The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P =.90) or overall survival (P =.89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P =.02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P =.009) but not in 5-year overall survival (65% versus 62%; P =.17). CONCLUSIONS: The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone.     

Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.     

Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.     

术后辅助放疗对ⅢA-N2期非小细胞肺癌的疗效探讨

目的 探讨术后辅助放疗对ⅢA-N2期非小细胞肺癌的疗效.方法 136例经病理学检查确诊为ⅢA-N2期的非小细胞肺癌患者,均行根治性手术及术后辅助化疗,辅助化疗后75例观察(A组),61例行辅助放疗(B组).结果 A组、B组1年总生存率分别为90.7%和98.4%,3年总生存率分别为41.2%和48.7%,5年总生存率分别为30.8%和33.7%(P=0.039).A组、B组1年无复发生存率分别为87.7%和95.1%,3年无复发生存率分别为59.9%和73.1%,5年无复发生存率分别为47.9%和65.8%(P=0.040).单因素生存分析提示:吸烟、临床N2期、T分期、阳性淋巴结个数、阳性淋巴结比例、N2淋巴结累及区域、辅助化疗疗程、行术后辅助放疗为预后因素.多因素生存分析提示:临床N2期、T分期、阳性淋巴结个数、行术后辅助放疗为独立预后因素.结论 ⅢA-N2期非小细胞肺癌中,术前临床诊断为N2期、T分期越晚、手术切除阳性淋巴结个数越多,预后越差;行术后放疗可提高局控率,延长总生存时间.     

Ⅳ期非小细胞肺癌同期化放疗的临床结果分析

目的 研究Ⅳ期非小细胞肺癌(NSCLC)同期化放疗的意义.方法 10年间收治经病理或细胞学诊断的Ⅳ期NSCLC患者300例,可分析病例214例,其中3周方案化疗同期放疗(同期A)98例、每周方案化疗同期放疗(同期B)18例、单纯化疗44例、单纯放疗37例和序贯化放疗17例.原发灶放疗采用常规分割和后程超分割的三维适形和常规放疗技术,肿瘤剂量为36～86 Gy.化疗中3周方案以铂类为基础联合紫杉醇、多西紫杉醇、长春瑞滨、依托泊甙等(21～28 d为1周期),每周方案采用顺铂联合紫杉醇或拓扑替康4-6周.结果 随访率为99%.同期A、同期B、单纯化疗、单纯放疗、序贯化放疗的1和2年生存率分别为41%和11%、16%和0、31%和7%、34%和10%、26%和3%(x2=11.18,P=0.025).分层分析显示同期A中采用三维适形技术、后程加速超分割方式、原发灶剂量≥70 Gy的较单纯化疗显著延长生存率,同期A中接受三维适形+后程加速超分割+≥70 Gy治疗的21例患者生存率显著优于单纯化疗,而且化疗≥2周期同期化放疗者的牛存率也较相同周期的单纯化疗者长.结论 化疗同期采用三维适形、后程加速超分割、≥70 Gy治疗原发病灶并对转移灶进行放疗可显著延长Ⅳ期NSCLC的生存期.     

Survival improvement of young patients, aged 16-23, with Hodgkin lymphoma (HL) during the last three decades

The prognostic factors, treatments and outcomes of 55 young adults (16-23 years old) with Hodgkin lymphoma (HL) treated in the Second Department of Internal Medicine Propaedeutic, Medical Oncology Unit, Athens University, over the past 25 years, are reviewed. Patients were treated with the chemotherapy regimens available at each time period which were MOPP (Group A; 1978-1987), MOPP/ABVD (Group B; 1988-1993) and BEACOPP or ABVD (Group C; 1994-2003). The eligible patients, received radiotherapy (RT) according to treatment consensus. Additionally, the patients were retrospectively divided according to risk factors (abnormal erythrocyte sedimentation rate (ESR), bulky mediastinal disease, > 3 involved nodes and extranodal involvement) into low [stage I/II; five patients (9%)], intermediate [stage III with adverse prognostic factors; 18 patients (33%)] and high risk categories [stages IIB bulky and III/IV; 32 patients (58%)]. A total of 21 (38%) patients experienced relapse (three intermediate and 19 high risk). The 5-year survival and the 5-year event free survival (EFS) figures were Group A: 65% and 53%, Group B: 80% and 65%, Group C: 100% and 88.5%, respectively, the improvements between Group B and C were statistically significant (p = 0.04 and p = 0.005, respectively) among the three time periods. The overall survival (OS) and EFS differed significantly between intermediate and high risk categories (OS: p = 0.04, EFS: p = 0.005). The sequential use of RT did not influence OS and EFS but there was a trend of improvement with RT in the later periods. Survival of young patients with HL is significantly improving most probably due to improved chemotherapy treatment and understanding of the risk factors. Current controversial issues surrounding this disease, including the role of radiotherapy, positron emission tomography (PET), bone marrow biopsy and stem cell transplantation are discussed.     

Induction chemotherapy with carboplatin and ftorafur in advanced head and neck cancer. A randomized study.

From 1987 to 1989, 42 patients with locally advanced squamous cell carcinoma of the head and neck (Stages III-IV, Mo) were randomized to receive radiotherapy (Group A) or three courses of induction chemotherapy followed by radiotherapy (Group B). There were 36 evaluable patients, 17 in Group A and 19 in Group B. The radiotherapy regimen was the same for both groups, 66-74 Gy total tumor doses with standard fractionation scheme of 2 Gy/day. The chemotherapy regimen was a combination of carboplatin 400 mg/m2 by intravenous bolus injection on day 1, and Ftorafur 1,000 mg/m2 orally once a day for 14 days. Cycles were given every 4 weeks. The complete response rate in Group A was 65%; in group B it was 31.5% after induction chemotherapy and 84% after radiotherapy. The 42-month actuarial overall survival rates were 34% for Group A and 47% for Group B (P = NS). Patients from both groups with a complete response had a significantly longer survival time than those with a partial response (P less than 0.001). No significant differences in disease-free survival were found between the two treated groups. The chemotherapy regimen was well tolerated, with moderate hematologic and gastrointestinal toxicity. Increased in radiation toxicity by chemotherapy was not observed.     

Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer.

The relationship between clinical response to DNA-damaging drugs and p53 and p21 status in patients with locally advanced transitional cell carcinoma (TCC) of the bladder was assessed. The response to intraarterial chemotherapy (IAC) comprising 100 mg / m(2) of cisplatin (CDDP) and 40 mg / m(2) of pirarubicin (THP) and the prognosis were assessed in 23 patients (the mean follow-up period was 19 months). The p53 gene status of tumors was analyzed at exons 5 - 8 using polymerase chain reaction-single strand conformation polymorphism analysis in 19 patients, and paraffin-embedded tumor sections were immunostained for p53 and p21 in 23 patients. The overall objective response rate (incidence of good responders) was 70%. The negative p53 group (n = 17) showed a significantly higher objective response rate than the positive p53 group (n = 6) (82% vs. 33%; P = 0.045). The p53 gene status or p21 staining status was not significantly associated with responsiveness. When the p53 and p21 immunostaining results were combined, good responders were more accurately predicted than by p53 staining status alone; the negative p53 / positive p21 group (n = 12) showed an objective response rate of 92%, which was significantly higher than that of the positive p53 and / or negative p21 group (45%, n = 11) (P = 0.027). Cause-specific survival of the negative p53 group was significantly superior to that of the positive p53 group (P = 0.015). Negative p53 / positive p21 immunostaining is a possible predictor of favorable chemotherapeutic response in patients with TCC of the bladder.