Age and bromodeoxyuridine labelling index as prognostic factors in high-grade gliomas treated with surgery and radiotherapy.

AIMS: To determine the prognostic value of proliferative potential and DNA ploidy in 72 brain tumours (36 grade III and 36 grade IV astrocytomas) using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. MATERIAL AND METHODS: All 72 patients underwent excision, mostly incomplete of the tumour. After surgery, eight patients received conventionally fractionated radiotherapy, 11 patients received accelerated radiotherapy, and 53 patients received hypofractionated radiotherapy. Tumour samples taken during surgery from each patient were incubated in vitro for 1 h at 37 degrees C with BrdUrd using the high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd labelling index [BrdUrd LI]), and the total DNA content were evaluated: RESULTS: The tumours showed variability in the BrdUrd LI values, which ranged from 0.3 to 19.1%. No difference was observed in mean BrdUrd LI between grade III and grade IV sub-groups. A significantly higher percentage of DNA aneuploidy was observed in grade III gliomas (69.4%) than in grade IV gliomas (52.8%). Univariate analysis showed that younger patients (< or = 51 years) (P = 0.021) with grade III gliomas (P = 0.030) and low tumour proliferation rate (BrdUrd LI < or = 2.7%, P = 0.028) had significantly higher 5-year survival rates. Tumour ploidy had no influence on patients' survival (P = 0.591). However, Cox multi-variate analysis showed that only age over 51 years, and high tumour proliferation rate (BrdUrd LI > 2.7%), were significant unfavourable prognostic factors in patient survival. CONCLUSION: In this study, independent prognostic factors for patients with high-grade gliomas treated with surgery and post-operative radiotherapy are age and tumour proliferation rate assessed according to the BrdUrd LI.

[Follow-up of 70 patients with advanced ovarian cancer after negative second-look laparotomy]. / Abstention thérapeutique dans les cancers ovariens avancés après laparotomie de second look négative.

OBJECTIVES: To analyze the results of treatment of 70 patients with stage III and IV ovarian cancer after second look laparotomy with negative findings and to identify causes of failure and prognostic factors. MATERIALS AND METHODS: Between 1985 and 1998, seventy patients with ovarian cancer stage III and IV were treated with surgery and at least six courses of chemotherapy with cisplatin doxarubicin and cyclophosphamide. Then a second look laparotomy was performed. RESULTS: The actuarial survival rate without evidence of disease was 50% at 5 years. Locoregional failure was observed in 31 patients (88%) and distant metastases in 9, but they were the sole reason for unsuccessful treatment in only 4 (12%). Adverse prognostic factors were: grade 3 differentiation, primary stage IIIC and IV, and residual infiltration exceeding 2 cm after first laparotomy. CONCLUSION: Our results are comparable with reports in the literature. The actuarial survival rate without evidence of disease at 5 years in patients with advanced ovarian cancer after second look negative laparotomy is 50%.

[Results of a randomized prospective trial comparing postoperative abdominopelvic radiotherapy with postoperative chemotherapy in early ovarian cancer]. / Résultats d'un essai prospectif randomisé comparant une radiothérapie abdominopelvienne postopératoire et une chimiothérapie postopératoire dans les cancers de l'ovaire précoces.

PURPOSE: In a prospective randomized trial, our aim was to evaluate and compare the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the treatment of early ovarian cancer. MATERIAL AND METHODS: Between 1990 and 1996, 150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients classified IC and IIA, who did not have evidence of residual disease after surgery, were randomized to two treatment branches: radiotherapy or chemotherapy (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30 Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In the chemotherapy branch (74 patients), there were six series of polychemotherapy separated with 3-weeks interval. In each series patients received association of cisplatin (50 mg/m2, d1), adriamycin (50 mg/m2, d1) and cyclophosphamide (500 mg/m2, d1). RESULTS: The tolerance of the treatment was good and comparable in both groups. In the radiotherapy branch, three late grade G3 intestinal complications were observed (three bowel obstructions, which required surgery in two cases). The actuarial survival rate without evidence of disease was 81% at 5 years for both groups. In our series we found that histological grade had the strongest influence on survival prognosis; it was the only significant factor in a multivariate analysis. Patients with grade G3 tumors had the worst survival. CONCLUSION: These data suggest that efficacy of postoperative radiotherapy and chemotherapy administered to our patients with early ovarian cancer gave approximately identical results.

Prognostic factors in retroperitoneal sarcomas: ploidy of DNA as a predictor of clinical outcome.

BACKGROUND AND OBJECTIVES: Radical surgery is the best mode of treatment of retroperitoneal sarcomas (RS); however, common recurrences are unpredictable. METHODS: For the better understanding of outcomes and possibilities of treatment retrospective analysis of different factors, including DNA content, was performed based on 70 patients. RESULTS: Leiomyosarcoma and liposarcoma were most common histologic types of classified sarcomas. Different kinds of resection were successfully performed in 51 patients (73%) and 35 of their available DNA specimens were analyzed. The actuarial 5- and 10-year survival rates in the resection group were 53% and 40%, respectively, with the median survival of 57 months. Patients with diploid resected tumors had a better 10-year survival rate (58%), than those patients with aneuploid tumors (25%,)--P<0.005. Those patients with low-grade sarcomas had a significantly longer survival than those with high-grade sarcomas (10-year survival rate: 44% compared to 29%). In the univariate analysis, adjuvant therapy, type of histology, type of surgery, location of tumor, and S-phase fraction had no influence on survival. In the multivariate analysis (Cox), only ploidy was an independent prognostic variable. Relative risk of death was over three times higher for aneuploid than for diploid tumors. CONCLUSION: Tumor ploidy should be analyzed in every case of retroperitoneal sarcoma for better assessment of prognosis and possible indication for adjuvant therapy.

[Radiotherapy for stage III, inoperable, asymptomatic small cell lung cancer. Final results of a prospective randomized study (240 patients)]. / Radiothérapie du cancer bronchique non à petites cellules de stade III, inopérable, asymptomatique. Résultats définitifs d'un essai prospectif randomisé (240 patients).

PURPOSE: To report the results of a prospective randomized study concerning the role of radiotherapy in the treatment of stage III, unresectable, asymptomatic non-small cell lung cancer. MATERIAL AND METHODS: Between 1992 and 1996, 240 patients with stage III, unresectable, asymptomatic non-small cell lung cancer were enrolled in this study, and sequentially randomized to one of the three treatment arms: conventional irradiation, hypofractionated irradiation and control group. In the conventional irradiation arm (79 patients), a dose of 50 Gy in 25 fractions in five weeks was delivered to the primary tumor and the mediastinum. In the hypofractionated irradiation arm (81 patients), there were two courses of irradiation separated by an interval of four weeks. In each series, patients received 20 Gy in five fractions in five days, in the same treatment volume as the conventional irradiation group. In the control group arm, 80 patients initially did not receive radiotherapy and were only observed. Delayed palliative hypofractionated irradiation (20-25 Gy in four to five fractions in four to five days) was given to the primary tumor when major symptoms developed. RESULTS: The two-year actuarial survival rates for patients in the conventional irradiation, hypofractionated irradiation and control group arms were 18%, 6% and 0%, with a median survival time of 12 months, nine months and six months respectively. The differences between survival rates were statistically significant at the 0.05 level. CONCLUSION: Although irradiation provides good palliation, the results are disappointing. The comparison of conventional and hypofractionated irradiation shows an advantage for conventional schedules.

Flow cytometric analysis of DNA ploidy and proliferative potential in brain tumours.

The proliferative potential and DNA ploidy in 203 brain tumours (27 astrocytomas grade I, 37 grade II, 80 grade III, and 59 grade IV) were investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. One to three tumour samples from each patient were incubated in vitro for one hour at 37 degrees C with bromodeoxyuridine (BrdUrd) using the high preasure oxygen method. After incubation, fixation and staining, the cell preparations were analysed by flow cytometry. The percentage of BrdUrd-labelled cells (BrdUrd Labelling Index, BrdUrdLI), the predicted potential doubling time (predTpot) and the total DNA content were evaluated. The percentage of unlabelled S-phase cells (SPF) and proliferative index (PI, the percentage of cells in S + G2 phases) were also estimated. DNA aneuploidy was found in 61.1% of high-grade (III-IV) and 50.0% of low-grade (I-II) astrocytomas. The tumours showed variability in the BrdUrdLI values which ranged from 0.2 to 15.8%. Significantly higher mean value for BrdUrdLI was shown in grade III-IV astrocytomas (3.4%), than in grade I-II astrocytomas (1.5%), p = 0.0068. Also significantly shorter mean predTpot was shown in high grade III-IV astrocytomas (28 days) than in low grade I-II tumours (51 days), p = 0.0096. However, no relationship was shown between other cell proliferation parameters and histological grade. The mean intratumoral variability calculated on the basis of BrdUrdLI values on 2-3 samples from each tumour amounted to 31.2% +/- SD 15.9%.

Altered therapy schedules in postoperative treatment of patients with malignant gliomas. Twenty year experience of the Maria Sklodowska-Curie Memorial Center in Kraków, 1973-1993.

Results of altered therapy schedules obtained in postoperative treatment of 294 patients with malignant gliomas over last 20 years are presented. During this period 135 patients received Conventional Irradiation and Chemotherapy (CICH), 61 patients received Conventional Irradiation (CI), 59 patients received Split Course High Fractional Dose Irradiation (SCHFDI), and 39 patients received Twice a Day Accelerated Irradiation (TDAI). Actuarial survival rates at 2, 3 and 5 years were 19%, 7%, 0% respectively for patients treated with CICH, and they were 21%, 10%, 0% for CI group, 24%, 12%, 0% for SCHFDI option and 15%, 8%, 0% for TDAI schedule. According to the Cox proportional hazard model, only age was significant factor in prognosis.

Multimodality treatment of noninflammatory stage IIIb breast cancer.

BACKGROUND AND OBJECTIVES: The 1990s have established the contribution of multimodality therapy in the management of IIIb noninflammatory breast cancer (IIIb NIBC), by reducing the odds of recurrence and death. METHODS: A total of 300 women with IIIb NIBC received a multimodality therapy. The treatment consisted of neoadjuvant chemotherapy [FAC (5-fluorouracil, Adriamycin, cyclophosphamide) regimen], radical (Halsted) mastectomy or modified (Patey mastectomy), postoperative radiotherapy, and adjuvant chemohormone therapy [FAC regimen + cyclophosphamide, 5-fluorouracil and methotrexate (CMF) regimen or Tamoxifen]. RESULTS: Complete or partial clinical response (CR or PR) after neoadjuvant chemotherapy was obtained in 83% patients. Ninety-nine patients (33%) survived 5 years without evidence of disease (NED). The uni- and multivariate analyses factors that had significant influence on the treatment results were: clinical response to neoadjuvant chemotherapy, pathological tumor size, and microscopical status of the axillary lymph nodes. CONCLUSIONS: We conclude that neoadjuvant FAC regimen chemotherapy is very effective in producing objective tumor regression and offers the benefit of radical mastectomy to patients with previously unresectable IIIb NIBC.

[The role of radiotherapy in the management of benign lymphoepithelial lesions]. / Rola radioterapii w leczeniu benign lymphoepithelial lesion.

Benign lymphoepithelial lesion (BLL) is observed as a diffuse or nodular enlargement of major salivary gland. In 80% it appears in woman in the sixth and seventh decade. The histopathologic appearance consist of a triad of parenchymatous atrophy, interstitial lymphocytic infiltration and epimyoepithelial islands. This disease co-exists in 50% of cases with connective tissue disorders. In patients with BLL the risk of the development of a malignant lymphoma may be as high as 40:1 in comparison to the control group. From 1960 to 1991 ten women with BLL in salivary glands were treated in Oncology Centre in Kraków. The disease was localized in parotid glands (8 pts), in submandibular glands (1 pt) and in parotid and submandibular gland (1 pt). In this group 3 patients were treated for the rheumatoid arthritis and in 1 women presented symptoms of Sjögren' syndrome. Exclusive surgical treatment was performed in 2 patients, 7 patients were treated with irradiation, and 1 patient received combined therapy: surgery and radiotherapy. The doses of irradiation were from 12 to 36 Gy given in 6 to 18 fractions. Complete remission was observed in 2 patients who received only surgical treatment. In group of 8 patients treated with irradiation and surgery and irradiation we have observed local control in six women after 1 series and in two women after 2 series of irradiation. During the observation malignancies developed in 4 patients between 11 to 39 months after radiotherapy. One patient developed cancer of salivary gland. In remaining 3 patients it was observed malignant lymphomas. Our results of therapy of BLL in salivary gland are similar to presented by the other authors and indicate the efficiency of local (surgical or irradiation) treatment.

[Exclusive radiotherapy in 250 cases of stage I-II cancers of the supraglottic larynx]. / Radiothérapie exclusive de 250 cancers du larynx sus-glottique stade I-II.

Two-hundred and fifty patients presenting with a stage I-II cancer of the supraglottic larynx were definitively treated with irradiation. The 5-year disease-free survival rate is 76%. Multivariate analysis reveals that the only statistically significant prognostic parameters are clinical stage (I versus II), and tumour site (epilarynx versus supraglottis).

[Cervical metastatic lymphnodes in laryngeal cancer patients following radiotherapy]. / Przerzuty w wezlach chlonnych szyjnych u chorych na raka krtani po leczeniu napromienianiem.

Analysis of the radiotherapy's failures in a form of metastatic lymph nodes was performed in the group of 373 laryngeal cancer patients. The authors point out that irradiation of large metastatic lymph nodes do not produce satisfying results. In the cases with supraglottic involvement there is a need of elective total neck irradiation.

[Treatment of stage I pure seminoma of the testis, value of prophylactic radiotherapy]. / Traitement des séminomes purs du testicule stade I, intérêt de la radiothérapie prophylactique.

Teleradiotherapy is the treatment of choice for stage I testicular pure seminoma. In this study of 130 patients, we compared the dose of 35 and 30 Gy given prophylactically. No statistically significant difference in survival was observed between the groups.

[Comparison of two methods of postoperative radiotherapy in anaplastic cerebral oligodendroglioma]. / Porównanie dwu metod pooperacyjnego napromieniania chorych na anaplastycznego skapodrzewiaka mózgu. Wstepne wyniki prospektywnego badania klinicznego.

Preliminary results of prospective clinical study--49 adult patients with histologically proven anaplastic oligodendroglioma received postoperative radiotherapy. Patients were randomized to two treatment arms: Conventionally Fractionated Radiotherapy (CFR) and Large Fractionated Radiotherapy (LFR). In CFR group the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks, then a 10 Gy "boost" in 5 fractions was delivered to the site of primary lesion in 5 days. In LFR group there were 3 courses of irradiation separated with one month interval. In each of the two first series the patients received 20 Gy in 5 fractions in five days to the whole brain, and in the third course, 10 Gy "boost" was delivered like in CFR regimen. The tolerance to treatment was good in both groups. Actuarial survival rates 2 and 4 years were 20% and 4% respectively for CFR group, and they were 27% and 0% respectively for LFR.

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial.

A prospective randomized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków. 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy. Patients were randomized to two treatment arms: Conventionally Fractionated Radiotherapy (CFR) and Hypofractionated Radiotherapy (HF). In the CFR group, the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks, then a 10 Gy 'boost' in 5 fractions in 5 days was delivered to the site of the primary lesion. In the HF group, there were 3 courses of irradiation separated by a one month interval. In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain, and in the third course, 10 Gy 'boost' in 5 days was delivered as in the CFR regimen. The tolerance to treatment has been found to be good in both groups. The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22% for CFR and 18% for HF. Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23% and 10%, respectively. This difference is statistically significant at the 0.05 level.

[Evaluation of post-irradiation reaction in patients after radiotherapy of laryngeal cancer]. / Ocena odczynów popromiennych u chorych na raka krtani leczonych napromienianiem.

The early and late local reactions after radiotherapy were evaluated by means of International Classification, in 345 laryngeal cancer patients. The positive correlation was found between the grade of reaction and radiation dose as so irradiated volume. The same tolerance was found in patients treated by X-therapy and cobalt teletherapy ++. The time for observation of the early reaction may be according to the authors elongated from 6 to 12 months.

[Results of adjuvant radiotherapy in patients with highly differentiated cerebral astrocytoma after non-radical surgery]. / Wyniki uzupelniajacej radioterapii chorych na wysoko zróznicowane gwiazdziaki mózgu po niedoszczetnych zabiegach operacyjnych.

In the years 1975-1982 49 patients received adjuvant tele gamma 60Co therapy because of highly differentiated cerebral astrocytoma after non-radical surgical intervention. 46 of them obtained the planned dose of 60 Gy in 30 fractions given during 6 weeks. In three patients the treatment has been discontinued because of bad tolerance. 20 patients (40%) survived 5 years. The differences of the probability of survival in separate histologic forms of astrocytomas have been not significant.

Results of postoperative irradiation of medulloblastoma in adults.

This study analyzes the results of combined surgery and radiation therapy in 13 cases of medulloblastoma in adults treated at the Institute of Oncology in Cracow between 1974-1980. There were 5 women and 8 men. The mean age of the patients was 22.4 years. The overall crude 5-year survival was 62%. Four patients developed recurrence at the primary site (in one case local recurrence was concurrent with pulmonary metastases). The posterior fossa dose in these patients was 2625, 3000, 4800, and 5000 cGy. All 5-year survivors received the posterior fossa dose ranging from 5000 to 5400 cGy. For optimal local control the posterior fossa dose of at least 5400 cGy is recommended, with prior irradiation of the whole cranio-spinal axis.

[Evaluation of radiotherapy failure in laryngeal cancer patients in several Polish medical centers during the years 1980-1982]. / Ocena niepowodzen leczenia napromienianiem chorych na raka krtani w kilku osrodkach krajowych w latach 1980-1982.

Analysis of the treatment failure was performed in the group of 634 laryngeal cancer patients treated by radiotherapy. It has been demonstrated that extensiveness of neoplasm and supraglottic region were disadvantageous as prognostic factors in radiotherapy patients.

[Analysis of the results of combined treatment of poorly differentiated brain gliomas]. / Ocena wyników skojarzonego leczenia niskozróznicowanych glejaków mózgu.

In a group of 139 patients with poorly differentiated brain gliomas controlled clinical trial was carried out for assessment of two methods of postoperative treatment. After possibly radical removal of the glioma the patients were treated by radiotherapy with 60Co teletherapy in doses of 60 Gy (30 fr) in depth during 6 weeks, and randomly chosen patients received also CCNU in one dose of 100 mg/m repeated at intervals of 6-8 weeks. The administration of CCNU failed to improve the therapeutic results. The median survival time in the whole group was 49 weeks. The survival rate after 1, 2 and 3 years was 45.4%, 22.8% and 14.9% respectively. The survival times of cases of glioblastoma multiforme were not significantly different from those of patients with other poorly differentiated gliomas independently of the treatment method. The complications were not troublesome.