Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: a secondary analysis of RTOG 85-27

Purpose: The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer.

Methods and Materials: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66–74 Gy in 33–37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (≥ 14.5 gm% for men, ≥ 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model.

Results: Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable.

Conclusion: Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.     

A case of asynchronous development of transitional cell carcinoma in the bladder and renal pelvis after prolonged cyclophosphamide therapy

Urinary bladder cancers occurring after prolonged cyclophosphamide therapy are being increasingly reported. Cyclophosphamide-induced cancer in the upper urinary tract is not, however, generally recognized. We report a case of asynchronous development of transitional cell carcinoma in the bladder and renal pelvis, after prolonged cyclophosphamide therapy for non-Hodgkin's lymphoma. To date, at least 8 cyclophosphamide-related cancers have been reported in the upper tract. These cases are reviewed briefly.     

Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: A phase II multicentric study

Background: Oxaliplatin is a new cytotoxic agent from the diaminocyclohexane family with proven antitumor activity against colon cancer cell lines. Activity in patients with colorectal carcinoma previously treated with 5-fluorouracil has been studied in three single-agent phase II trials, showing a reproducible response rate of 10%. Here we report a phase II trial with oxaliplatin as a first-line chemotherapy for metastatic colorectal cancer.Patients and methods: Twenty-five patients were entered in the study. All of them had metastatic disease without previous chemotherapy, and at least one lesion had to be measurable by computed tomography (CT). Therapy consisted of a two-hour infusion of oxaliplatin at a dose of 130 mg/m² every 21 days.Results: The overall response rate determined by investigators was 20% (95% CI, 6.8%–40.7%). Eight patients (32%) had stable disease. The median time to disease progression in responders was six months (range four to nine). The median progression-free survival was four months and median overall survival 14.5 months (95% CI, 10–20 months). The main toxic effects were peripheral neuropathy (92%) and laryngopharyngeal dysesthesia (75%). No severe grade 3–4 neurotoxicities (NCI-CTC) were found. Gastrointestinal and hematological toxicities were mild.Conclusions: Oxaliplatin is an active agent in first-line chemotherapy for advanced colorectal cancer. It was well tolerated, caused no toxic deaths, had low hematotoxicity, well controlled gastrointestinal toxicity, and frequent but mild peripheral neurological symptoms. Therefore, it is of interest to associate oxaliplatin with other active compounds.     

Assessment of vascularity in breast carcinoma by computer-assisted video analysis (CAVA) and its association with axillary lymph node status

Case-control methodology was used to evaluate the significance of vascularity in small breast carcinomas with regard to the presence or absence of axillary lymph node metastases. Vascularity was assessed in 32 axillary node positive primary breast tumours (LN+ve) less than 2 cm in size and compared with 56 control axillary node negative primary tumours (LN–ve), which were matched for histological type and grade and tumour size. This study design employed computer-assisted video analysis (CAVA) to assess the total blood vessel perimeter (BVP), total blood vessel area (BVA), and total blood vessel density (BVD) throughout a tissue section that encompassed an entire cross section of the tumour and its immediate periphery. The BVA and BVD in these tumours were not significantly different between LN+ve and LN–ve groups. The LN–ve carcinomas had, on average, a significantly (P < 0.05) higher total BVP (3355 µm/mm²) than LN+ve tumours (2771 µm/mm²). 'Hot spot' areas were also independently assessed by two pathologists and the same areas measured by CAVA. A strong correlation (P < 0.001) between the two methods of assessment of BVD of the neovascular 'hot spots' was found; however, no association with axillary lymph node metastasis was found using either method of assessment. In conclusion, vascularity assessed by either blood vessel density or blood vessel size in primary invasive breast cancers less than 2 cm in diameter showed no association with axillary lymph node metastasis; in fact a negative association was found with total BVP of whole tumour sections and BVD in 'hot spots' using CAVA. Further, this study has established a computer-assisted method of quantifying vascularity in solid neoplasms and is a positive step towards a standardised approach to this diverse and methodologically variable area.     

Phase II study of Temodal in the treatment of patients with advanced nasopharyngeal carcinoma

Purpose: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal carcinoma was undertaken to determine the efficacy and safety of the drug in this population. Methods: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study. One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m² daily on days 1–5 every 28 days. Results: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease after 2 (84.6%) or 4 (15.4%) courses. Conclusion: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma. Received: 9 January 1998 / Accepted: 4 February 1998     

喉鳞癌组织中Bcl—2和P53蛋白表达及意义

为了探讨ｂｃｌ－２，Ｐ５３在喉鳞癌组织中的表达情况，预后的意义，我们应用免疫组化ＬＳＡＢ法对５３例喉鳞状上皮细胞癌组织进行ｂｃｌ－２，Ｐ５３基因蛋白表达的测定。结果显示：（１）４７．１７％的喉癌中检出突变型Ｐ５３蛋白，在部分喉癌旁不典型增生上皮中可见Ｐ５３蛋白表达，癌旁组织细胞已发生Ｐ５３基因突变可能是术后复发的根源，突变型Ｐ５３蛋白过度表达是喉癌发生的早期事件。     

肾透明细胞癌中PCNA和T淋巴细胞的免疫组化研究

应用免疫组化的方法，检测增殖细胞核抗原（ＰＣＮＡ）和Ｔ淋巴细胞在５２例肾透明细胞癌中的阳性表达，结果显示ＰＣＮＡ指数与肿瘤核分级存在相关性，与分期无相关性；ＰＣＮＡ－ＬＩ≥２０％组的生存率明显低于ＰＣＮＡ－ＬＩ＜２０％组（Ｐ＜０．０５）；Ｔ－ＬＩ≥１０％组生存率明显高于Ｔ－ＬＩ＜１０％组（Ｐ＜０．０５）；与肿瘤核分级、分期无相关性。提示ＰＣＮＡ－ＬＩ、Ｔ－ＬＩ可以作为肾透明细胞癌预后的参考指标。     

ras基因的表达与胃癌细胞生物学特性的相关研究

为研究ｒａｓ基因在胃癌中的表达，采用组织化学、免疫化学和自动图像分析方法，检测了５４例胃癌切除标本的ｒａｓ基因表达、癌细胞核形态参数和ＤＮＡ含量及倍体分布类型。发现胃癌细胞ｐ２１表达水平随着ＤＮＡ含量不断增多、倍体成倍增加而逐渐下降。表明ｒａｓ过度表达主要出现在细胞表型发生明显转化之前。此外，发现胃癌细胞ｐ２１的表达水平与癌细胞核形态参数、癌肿大小、有无淋巴结转移均无关。     

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively.     

Infrequent Mutations of the hOGG1 Gene, That Is Involved in the Excision of 8-Hydroxyguanine in Damaged DNA, in Human Gastric Cancer

DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh⁸Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser³²⁶ vs. hOGG1-Cys³²⁶) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys³²⁶ allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.