Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.     

Reproductive performance of patients with gestational trophoblastic disease in Hong Kong

The reproductive performance of 110 patients who had had gestational trophoblastic disease was reviewed. There were 160 pregnancies and their outcomes were similar to that of the general population. The subfertility rate was also comparable to the general population. The high rate of failure of contraception resulting in a high rate of conception during the first year of follow-up warrants special attention. Reasons for the high failure rate and ways of prevention are discussed. Reasons for the deliberate delay in attempts to conceive in patients after the full year of postmolar human chorionic gonadotropin (hCG) surveillance were explored.     

Maternal determinants of birthweight in normal pregnancy

Partial and multiple regression analysis was performed to find out the correlation between birthweight and maternal anthropometric variables. Pearson regression analysis revealed significant dependence of birthweight on gestation of pregnancy, maternal weight, symphysis-sternal distance and height, but not on armspan and skin thickness. However, the only maternal variable bearing significant influence on birthweight in partial regression analysis was bodyweight. The effects of maternal determinants on birthweight, though some of them were statistically significant, were clinically unimportant.     

Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience

AIM: Radiotherapy has been shown to improve local control in combination with limb-sparing or conservative surgery in the management of localised soft tissue sarcoma. Our centre's treatment protocol is to offer preoperative external beam radiotherapy (50.4Gy in 28 fractions) followed by surgery four to six weeks later. The aim of this study is to review the treatment outcome and toxicity of patients treated with this protocol. METHODS: Consecutive patients with localised extremity or truncal soft tissue sarcoma who presented between January 1996 and December 2000 and treated with preoperative radiotherapy followed by limb-sparing surgery were reviewed. Patients with recurrent disease or metastatic disease at diagnosis and patients below the age of 16years were excluded. Local and distant recurrence, overall survival and treatment toxicity were analyzed. RESULTS: Sixty-seven cases were identified (41 males and 26 females). The median age was 52years (range 17 to 82). The majority (79%) had tumours located in the lower limb. The most common histological diagnoses were malignant fibrous histiocytoma and liposarcoma. The median follow-up was 4.1years (range 0.6 to 6.9). There were six local recurrences, two of which were successfully salvaged. Twenty patients developed distant metastases. The estimated 5-year actuarial local recurrence free, distant recurrence free and overall survival were 93%, 68% and 73% respectively. Acute radiotherapy toxicity and wound complications were acceptable and late toxicity was uncommon. CONCLUSION: Preoperative radiotherapy followed by surgery provides effective local control in the management of soft tissue sarcoma.     

Circulating Epstein-Barr virus DNA in serum of patients with lymphoepithelioma-like carcinoma of the lung: a potential surrogate marker for monitoring disease.

PURPOSE: The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA. EXPERIMENTAL DESIGN: Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2). RESULTS: Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring. CONCLUSIONS: This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.     

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.     

Dose-Tumor Response for Carcinoma of Cervix: An Analysis of 594 Patients Treated by Radiotherapy

This is a retrospective study of 594 histologically proven carcinomas of the uterine cervix treated with radiotherapy alone between January 1970 and December 1986. The age of this group of patients ranged from 22 to 86 years, and the median age was 57 years. There were 544 (91.6%) patients with squamous carcinoma and 36 (6.1%) with adenocarcinoma. There were 24 (4.0%) patients who were treated by two sessions of intracavitary brachytherapy only using intrauterine tandem and vaginal ovoids; 513 (86.4%) patients received whole pelvis irradiation followed by two sessions of brachytherapy at 1-week intervals, with or without additional boost to the parametrium. The dose to point A ranged from 40 to 100.9 Gy for the patients with stage IB to IIIB disease. The 5- and 10-year survival for stages IB, IIA, IIB, IIIA, and IIIB were 90.0, 82.1, 72.0, 50.0, 51.5, and 86.9, 71.0, 67.5, 41.7, and 46.9%, respectively. There was no long-term survivor for stage IV disease; the median survivals for patients with stages IVA and IVB were 15.2 and 9.3 months, respectively. Dose response was demonstrated for stages IIB and III tumors; dose to point A greater than 85 Gy was associated with better central control (P = 0.0036 and 0.0234, respectively). However, further increase in dose to point A beyond 85 Gy was not associated with improvement in central control (P = 0.3128 and 0.3394, respectively, for stages IIB and III). It was also found that the occurrences of rectosigmoid and bladder complications were correlated with the rectal and point A dose. Thus, for these patients, there is no need to increase the dose to point A beyond 85 Gy so that the risk of radiation sequelae can be cut down.     

Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules

Vinflunine is a novel Vinca alkaloid presently in Phase I clinical trials. In preclinical studies, it exhibited superior antitumor activity to that of other Vinca alkaloids, including vinorelbine from which it was synthetically derived. Vinca alkaloids appear to inhibit cell proliferation by affecting the dynamics of spindle microtubules. Here we have analyzed the effects of vinflunine and vinorelbine on microtubule dynamic instability and treadmilling and found that these newer drugs exert effects on microtubule dynamics that differ significantly from those of the classic Vinca alkaloid, vinblastine. The major effects of vinflunine and vinorelbine on dynamic instability were a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. In marked contrast to the action of vinblastine, they neither reduced the rate of shortening nor increased the percentage of time the microtubules spent in an attenuated state, neither growing nor shortening detectably. In addition, vinflunine and vinorelbine suppressed treadmilling, but less strongly than vinblastine. The diverse actions of these drugs on microtubules are likely to produce different effects on mitotic spindle function, leading to different effects on cell cycle progression and cell killing. Nontumor cells with normal checkpoint proteins may tolerate the relatively less powerful inhibitory effects of vinflunine and vinorelbine on microtubule dynamics better than the more powerful effects of vinblastine. Thus the unique constellation of effects of vinflunine and vinorelbine on dynamic instability and treadmilling may contribute to their superior antitumor efficacies.     

Hepatic arteriogram for gestational trophoblastic tumor: is it useful?

The presence of liver metastasis will be staged as IV in the FIGO 1992 Gestational Trophoblastic Tumor (GTT) staging. This study was to determine the role of hepatic arteriogram (HAG) in the management of GTT. It is a retrospective analysis of 309 patients treated from 1981 to 2001. Patients were restaged according to the FIGO 1992 classification with or without taking into account the HAG result. Outcome measures including mortality, drug resistance and recurrence of disease, as well as treatment with and without the HAG result were compared. Eighty-one (26.2 percent) patients had HAG and 11 (3.6 percent) also had ultrasound (USG) features of liver metastasis. Interval between diagnosis and treatment were significantly different between USG and HAG positive groups (Mann-Whitney U test, P < 0.05). Seventeen (5.5 percent) of the 309 patients died of the disease and 7 (41.2 percent) of them had liver metastasis. Three (27.3 percent) of the 11 patients who had USG features of liver metastasis died of the disease; mortality is significantly higher than those without USG features of metastasis (Chi-square test, P < 0.05). Patients classified as medium to high risk with or without taking HAG as a feature of liver metastasis were associated with higher mortality and recurrent rate (Chi-square test, P < 0.05). On the other hand, the chance of drug resistance was higher in the medium to high risk group after reclassifying all HAG positive patients as negative for liver metastasis (Chi-square test, P < 0.05). HAG evidence of liver metastasis did not correlate with patient mortality. HAG was not an appropriate investigation in the management of GTT.