Combined postoperative radiotherapy and pcv-chemotherapy (ccnu, procarbazine and vincristine) in managing anaplastic astrocytoma - a report of a long-term follow-up.

Postoperative radiotherapy together with CCNU, procarbazine and vincristine (PCV-chemotherapy regimen) were analysed in patients with histologically confirmed anaplastic astrocytoma. This report evaluates the long-term survival correlated with important prognostic variables. Patients who received more than 6 courses of the PCV-chemotherapy had significantly longer survival (P=0.03). Age and performance status, identified as important prognostic factors in previous studies, are confirmed in this analysis.

Postoperative 5-fluorouracil plus levamisole combined with radiation therapy for high risk rectal cancer patients.

Adjuvant chemotherapy in rectal cancer patients is aimed at decreasing the relapse rate of the disease, increasing the disease-free and the overall survival of the patients. The combinations of radiation therapy and several drugs have been tested, but the efficacy of 5-fluorouracil plus levamisole in rectal cancer is not determined yet. Sixty-two consecutive Dukes' B2 or C rectal cancer patients were enrolled into a prospective phase II study. Within 4 to 6 weeks following en-block resection of the tumor and lymphatics, adjuvant chemotherapy had to be started. Combination of 5-FU 375 mg/m(2)/day was given intravenously over 15-20 min for 5 consecutive days, every 4 weeks for 1 year. Levamisole 50 mg t.i.d. was administered orally during the first 3 days of each course of chemotherapy. Radiation therapy included 50 Gy, given by a linear accelerator 8 MV, to a pelvic BOX field. Dose per fraction was 1.8-2.0 Gy daily, administered for 5 consecutive days a week. Follow-up time of the whole group ranges from 7 to 53 months (median 18). Failure rate was 32.3%. The most common site for first relapse was the liver followed by recurrence in the pelvis or the surgical bed. Age, sex, tumor grade and number of involved lymph nodes were not associated with rate nor with site of relapse. Fifty-five percent of the relapses were observed in patients during the year of the adjuvant treatment. Toxicity included diarrhea (33.9%), nausea and vomiting (19.4%), weakness and mucositis. The disease-free survival rate for a median follow-up of 18 months in our study is 75%. The 3.5 year disease-free survival is 67% for the whole group. Our phase II study results point to the feasibility and acceptable toxicity of post-operative combination of 5-FU plus low-dose levamisole and radiation therapy in rectal cancer patients.

Vinorelbine-related acute cardiopulmonary toxicity.

Three cases of possible acute cardiopulmonary toxicity following the administration of vinorelbine are reported. The symptoms mimicked acute cardiac ischemia. However, neither ECG changes nor elevations of serum enzymes were observed. The outcome is favorable in 90% of patients developing this adverse event. The putative mechanism remains to be elucidated.

Treatment of disease-negative but mucin-like carcinoma-associated antigen-positive breast cancer patients with tamoxifen: preliminary results of a prospective controlled randomized trial.

Increasing levels of tumor markers such as carcinoembryonic antigen, mucin-like carcinoma-associated antigen (MCA), CA 15.3, and monoclonal antibody H23 in breast cancer patients following the treatment of the primary disease and adjuvant radiation and chemotherapy reflect subclinical development of metastatic disease. Overt metastatic disease is usually incurable and prolongation of life at this stage is impossible, and the treatment is only palliative. The efficacy of tamoxifen, a least-toxic agent, in the treatment of early and minimal metastatic disease detected only by increasing serum levels of MCA was studied prospectively in a randomized study. Our preliminary, albeit encouraging, results showed that the rate of relapse within a median follow-up period of 11 months was 24.1% in the control arm as compared with 0% in the tamoxifen arm (Fisher's exact test, P = 0.012). None of the patients with a relapse had positive progesterone receptors (PR). We may carefully conclude that early treatment may be warranted in young patients with negative PR and continuously increasing serum levels of the marker.

Postoperative irradiation combined with chemotherapy for high-risk rectal cancer patients.

In a prospective open-study we evaluated the combination of radiation therapy and adjuvant 5-FU plus levamisole in controlling Modified Astler-Coller (MAC) B2 or C rectal cancer following a curative-intended surgery. Sixty-four consecutive rectal cancer patients were treated by adjuvant radiation therapy (Linac 8 MV, 50-50.4 Gy to an isocentric pelvis brick volume in 5 fractions per week each of 1.8-2 Gy), and 12 monthly courses of 5-fluorouracil (375 mg/m(2)/day for 5 consecutive days) plus levamisole (50 mg t.i.d. for 3 days). Within a median follow-up period of 36 months, 19 patients (29.6%) experienced relapses. The 3-year-DFS of MAC B2 patients was 82%, compared with 60% in MAC C. Early radiation treatment was not associated with a higher proportion of relapses, while late radiation therapy initiation was associated with a significantly higher proportion of relapses. Early radiation therapy, not later than following the 2nd to 4th course of chemotherapy, is associated with the more acceptable proportion of relapses.

Tamoxifen for disease-negative but MCA-positive breast cancer patients.

Increased levels of mucin-like carcinoma-associated antigen (MCA) in breast cancer patients with no evidence of disease following the treatment of the primary disease created a dilemma of 'to treat' or 'wait and see'. One might assume that early treatment of clinically undetectable disease on the basis of an elevated serum level of a sensitive and reliable tumor marker, may improve the treatment results, and even prolong the patient's survival. 'Wait and see' on acceptance of the notion that even early metastatic disease, still manifested only by uprising MCA levels, is incurable, and treatment should be kept in reserve for palliation of symptomatic disease. Sixty-one breast cancer patients with increasing MCA levels but without evidence of metastatic disease were randomized for tamoxifen 20 mg b.i.d. or to follow-up till relapse. The results for a median follow-up period of one year were encouraging. The non-treated patients experienced a significantly higher relapse rate (24.1%) than the tamoxifen-treated subjects (0%; p=0.012). The results for a median follow-up of 5 years were disappointing. The overall relapse rate was 22.2%. The relapse rate among the control patients was 25.8% while in the treatment arm it was 17.4% (p=0.46). The event-free survival and the pattern of relapse were similar in both arms. Tamoxifen may therefore be reserved for overt metastases, and not wasted on asymptomatic subclinical disease. It seems that there is no yield in terms of event-free survival for MCA measurements in breast cancer patients during the 5-year follow-up period.

Clips and scar as the guidelines for breast radiation boost after lumpectomy.

BACKGROUND AND AIMS: Breast-conserving therapy in early breast cancer is equally effective as mastectomy, with advantages of cosmesis and quality of life over mastectomy. Local control is improved when entire breast irradiation is combined with a radiation boost to the tumour bed. METHODS: Localization of the tumour bed was compared in 45 consecutive patients using surgical scar and radiopaque clips placed intra-operatively in the lumpectomy cavity. RESULTS: The area (A) of the radiation boost field and volume (V) of the tumour bed, designed on the basis of scar (AS and VS), were 1.4 times larger than those designed on the basis of the clips (AC and VC). AS and VS missed about one-quarter of the tumour bed which had been delineated by clips intra-operatively, while about one-half of it encompassed tissues beyond the AC and VC. CONCLUSIONS: A boost planned by scar dimensions can miss a substantial portion of the tumour bed, compromising local control. On the other hand, a substantial amount of breast tissue beyond the tumour bed can be unnecessarily irradiated, compromising cosmetic treatment results. Thus, the scar provides an inadequate landmark for radiation boost planning in breast-conserving therapy.

Cerebral metastatic melanoma: correlation between clinical and CT findings.

Thirty patients with malignant melanoma and cerebral metastases confirmed by CT were studied. Metastases were classified according to their size: < or = 1 cm (group A), 1.1-4 cm (group B), and > 4 cm (group C), in order to assess the clinical course of the disease and predict the response to treatment with fotemustine. Group B lesions were the most common, independent of the site of the primary tumour, except for patients with rectal melanoma. Group C metastases were least common and were usually solitary. Asymptomatic patients usually had group A metastases, whereas those with non-specific complaints, hemisyndrome or neurobehavioural changes usually had group B metastases. The time from diagnosis of the primary tumour to discovery of disease in the CNS was significantly longer for those who had group A lesions, compared with those who had groups B or C lesions (P < 0.0001). Solitary lesions usually belonged to groups B or C, whereas multiple lesions belonged mainly to groups A or B. All the responders to fotemustine has mainly cortical, group A or group B lesions. Patients with group C lesions or leptomeningeal spread did not respond to fotemustine. Our findings suggest an association between the size of the cerebral metastatic lesion from malignant melanoma and clinical parameters characteristic of tumour behaviour.

Metastatic disease of the cavernous sinus: contribution of computed tomography and magnetic resonance imaging to diagnosis.

The clinical presentation of metastatic disease to the cavernous sinus includes ophthalmoplegia, pain and sensory deficit along the optic or maxillary branches of the trigeminal nerve. The role of a CT scan and magnetic resonance imaging in the diagnosis is discussed. It was found that magnetic resonance imaging is superior to CT scan in demonstrating the cavernous sinus and pontine borders, especially in lymphomatous involvement of these structures.

[Serum lactate dehydrogenase isoenzyme spectrum in malignant neoplasm patients]. / Izofermentyi spektr laktatdegidrogenazy syvorotki krovi bol'nykh zlokachestvennymi opukholiami.

The isoenzymic spectrum of lactate dehydrogenase of blood sera was studied in 170 patients with malignant and benign tumors, chronic inflammatory lesions and in healthy persons. The characteristic changes in patients with malignant tumors were as follows: an increased activity of slow fractions and a decreased one in rapidly migrating fractions. The level of the 5th isoenzyme activity and the frequency of its increased activity in serum correlated well with the degree of cancer spread. The determination of a percentual content of the isoenzyme may be used as a supplementary test for diagnosing metastic involvement of the liver. The examination of the serum lactate dehydrogenase spectrum in patients with benign tumors and chronic inflammatory disease revealed no changes characteristic of malignant neoplasms.

[Serum enzymatic activity in oncological patients treated with carminomycin]. / Aktivnost' nekotorykh fermentov syvorotki krovi u onkologicheskikh bol'nykh pri lechenii karminomitsinom.

Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible.

Progesterone receptor status and tumor size as possible indicators of axillary lymph node involvement in T1 carcinoma of the breast.

Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better definition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p = 0.026 in univariate and p = 0.0024 in multivariate analyses). Progesterone receptor status also correlated significantly (p = 0.0008 in univariate and p = 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be significant (p 0.018) only in univariate analysis. These findings contribute to the ongoing search for confident selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.

Prognostic importance of advanced age in aggressive non-Hodgkin's malignant lymphoma.

The importance of age as a prognostic factor in aggressive non-Hodgkin's malignant lymphoma (NHL) remains controversial. It is not clear whether age is an independent factor, reflecting the limited physiologic reserves of the patient, and leading in any treatment conditions to the poorer treatment outcome. This study was aimed at assessing the influence of age on treatment results in NHL patients. Therefore, the records of 40 patients with histologically confirmed NHL of intermediate and high-grade malignancy, according to the Working Formulation, who were treated by Adriamycin-containing chemotherapy, were retrospectively reviewed. There were 25 patients above 60 years of age and 15 patients below this age. Myelotoxicity was observed in 60% of the patients in the younger and in 48% patients in the older age group. The median time to dose-limiting toxicity, average percentage of projected dose intensity for all drugs, and percentage of projected dose intensity did not differ significantly in the two groups. Complete remissions (CR) were obtained in 67 and 64% of the younger and older groups, respectively. Progressive disease was observed during the treatment in 20% of the patients in each age group. Median survival was 36.5 and 32 months in the younger and older group, respectively. In conclusion, age alone is not an absolute predictor of survival of treated elderly patients with aggressive NHL. Dose rate, tolerance of treatment and achievement of CR are additional important prognostic factors. Dose intensity should not be automatically reduced at the beginning of the treatment, especially now that growth factors are available.

Primary liposarcoma of the mediastinum.

Patient. A 62-year-old man presented with effort dyspnea, non-productive cough and weakness of 4 month duration. He had no findings on physical examination.Discussion. Chest X-ray revealed a large mass in the left anterior mediastinum. Computerized tomography of the chest showed a well-delineated homogeneous mediastinal mass with fat-equivalent density and a small pleural effusion. Fiberoptic bronchoscopy revealed narrowing of the left main bronchus, secondary to external compression. The bronchial mucosa was normal and brush cytology was negative. A CT-guided fine needle aspiration (FNA) of the mass yielded fragments of cells embedded in myxoid background material and closely packed atypical lipoblasts, compatible with liposarcoma. The patient underwent a left lateral thoracotomy and margibnal resection of the mass. The histopathological examination confirmed the diagnosis of mixed-type liposarcoma, consisted of myxoid and pleomorphic liposarcoma. Postoperative two-field radiation therapy was delivered to the mediastinum for a total midplane dose of 40 Gy. After a disease-free interval of 8 months the disease recurred in the mediastinum and pleura. Palliative chemotherapy achieved a short duration partial response but the patient succumbed to local recurrence 2 years after the diagnosis.

Phase II study of recombinant interferon alpha-C in patients with metastatic renal cell carcinoma.

Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease-free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study.