Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry.

BACKGROUND: Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited. METHODS: We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions. RESULTS: Median age at diagnosis of BMs was 56 years (22-90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%), whereas the percentage of patients with luminal-like tumours increased (28%-34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval [CI]: 6.7-8.0 months). One-year survival rate was 37.7% (95% CI: 35.2-40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0-13.4) compared with 5.9 months (95% CI: 5.0-7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9-5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001). CONCLUSIONS: Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.

Clinical, molecular- and cytogenetic analysis of a case of severe radio-sensitivity.

In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.

[Radiotherapy for endometrial cancer]. / Radioonkologische Optionen beim Endometriumkarzinom.

Over the past decades, incidence, therapy and overall survival of endometrial cancer have changed considerably. Since 1977, surgical treatment has been preferred. In 1988, for example, only 5 % of the patients, mainly inoperable, were treated by primary irradiation. Patients, who undergo surgical treatment alone, have a significantly better outcome than patients with surgery and adjuvant irradiation. Patients treated by primary irradiation show the worst survival outcome, because of the selection bias for advanced stages. This observation even holds true, if adjusted for age and therapy modality. Modern irradiation technology may offer curative treatment options even in cases with advanced stages or severe co-morbidity, as well as locoregional recurrence.

[Remembering DEGRO 2000-evaluation of the refresher course survey]. / Nachlese zum DEGRO 2000-die Auswertung der Refresherkurs-Umfrage.

BACKGROUND: Refresher courses as presented at the annual DEGRO meeting are important parts in the continuous training of radiotherapists. For further quality improvement, knowledge about the participants' needs is essential. METHODS: During the DEGRO meeting 10/2000 in Munich, participants of refresher courses were encouraged to grade the presentations with regard to six questions with marks from 1 ("very good") to 6 ("not acceptable"). Free comments were welcomed. The individual results were handed over to future organizing committees and the speakers themselves, cumulative results can be read up in the present note. RESULTS: Approximately 1,000 participants of refresher courses filled in 381 questionnaires concerning 24 different training sessions. Altogether 48.5% of all answers said "very good", 31.7% "good" and 11.1% "satisfactory" (all worse marks together 3%, no statement in 5.7%). Free comments dealt mainly with handouts and a later starting time for the refresher courses than 7:30 a.m. CONCLUSION: Participants of the annual DEGRO meeting show a great amount of interest in refresher courses and seem to be quite content with the present findings. First steps are taken to get the proposals under way.

Chromosomal aberrations induced in mice bone marrow by treating with cisplatin and irradiation.

BACKGROUND: The aim of this study was to quantify the combined effect of cisplatin and radiation on chromosomal damage with emphasis on the time interval between cisplatin and radiation. METHODS AND MATERIALS: Bone marrow of female NMRI-nu(+) mice was taken as a model system for a highly proliferative tissue irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally (i.p.) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before and after radiation. Bone marrow and metaphases were prepared according to standard procedures. RESULTS: The percentage of aberrant metaphases after radiation or cisplatin alone increased in a dose-dependent manner (sigmoidal dose-response curve). Combining both modalities led to additive values at all time points for the percentage of aberrant metaphases. Borderline significant (p < 0.05) supraadditive effects were found 2 hours before or 1 hour after irradiation. However, a supraadditive percentage of aberrant chromosomes was found only at 2 or 1.5 hours with cisplatin before irradiation indicating the dependence of supraadditivity on the chosen parameter. CONCLUSION: It is doubtful to expect a true supraadditive or "radiosensitizing" effect, e.g. in the clinical setting from combined treatment with cisplatin and radiation. Rather, cisplatin might act as an independent cytotoxic agent.

Combined fractionated external beam radiotherapy and low-dose-rate iodine-125 seeds in an experimental tumor system.

BACKGROUND: To quantify the effect of implanted low-dose-rate iodine seeds combined with fractionated external beam radiation on local control rates in an experimental tumor system. MATERIALS AND METHODS: Experiments were done on the rhabdomyosarcoma R1H of the rat transplanted s.c. into the back of male WAG/Raj albino rats. Tumors were irradiated with 200 kVp X-rays with 2 Gy/fraction 5 times weekly. The total dose of the external beam irradiation varied between 60 and 98 Gy for external beam radiotherapy alone and 10 Gy to 82 Gy for combined external beam radiotherapy and iodine seeds. One to 4 iodine seeds with a median activity of 21.05 MBq were permanently implanted 3 days before the start of external radiotherapy or 6 and 7 iodine seeds alone were used. The median tumor volume at the start of treatment was 0.12 cm3. Local tumor control rates were determined and TCD37% values were calculated applying the maximum likelihood method. RESULTS: With increasing number of implanted iodine seeds the TCD37% (of external beam irradiation) decreased. With external beam radiotherapy alone the TCD37% amounted to 103.2 Gy (95% CI, 101.3 to 105.1 Gy) decreasing to (externally applied doses) 69.7 Gy (63.7 to 74.7 Gy) after 1 implanted iodine seed and further to 31.6 Gy (25.6 to 37.6 Gy) after 4 implanted iodine seeds. The effective dose (equivalent to external dose) per iodine seed decreased with increasing number of implanted iodine seeds. One iodine seed gave an effective dose of 33.5 Gy (28.5 to 39.5 Gy) decreasing to 17.9 Gy (16.4 to 19.4 Gy) after 4 iodine seeds. CONCLUSIONS: The combined treatment of tumors with implanted low-dose-rate iodine seeds and external beam irradiation can decrease the total dose of the external beam irradiation and, hence, offer the possibility of considerable dose sparing of normal tissues without compromising local tumor control rates.

Influence of the hypoxic subvolume on the survival of patients with head and neck cancer.

PURPOSE: Tumor hypoxia is regarded as an important factor influencing radiation response, disease-free, and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN). This study was performed to reevaluate the prognostic significance of the "classical oxygenation parameters" hypoxic fraction (percentage of pO2 values < 5 mmHg or < 2.5 mmHg, respectively) and median pO2, and to determine the influence of a new radiobiological factor. This factor was termed the "hypoxic subvolume" (HSV) and was defined as percentage of pO2-values below 5 mmHg multiplied by the total tumor volume. The rationale of this parameter was to quantify approximately the amount of hypoxic tissue which should be correlated to the number of hypoxic cells in the tumor. It is obvious that a tumor of 100 cm3 with a hypoxic fraction of 20% (HSV = 20 cm3) contains more hypoxic cells than a tumor of 1 cm3 with a hypoxic fraction of 50% (HSV = 0.5 cm3). METHODS AND MATERIALS: Pretreatment pO2 was assessed in 59 patients with SCCHN with the Eppendorf histograph, and pretreatment volume was determined by ultrasonography (lymphnode metastases) and computer tomography (primaries). All patients were referred to our departments for radiotherapy (n = 27, median dose 70 Gy) or radiochemotherapy (n = 32; 5-FU, mitomycin C, median dose 70 Gy), respectively. All parameters were evaluated using the Kaplan-Meier analysis, and significance was assumed at a p-value of < 0.05 (log-rank test, Cox-Mantel). A multivariate analysis was performed to control for confounding factors. The median follow-up was 233 days. At the time of the evaluation, 34 of the 59 patients were dead. RESULTS: In univariate analyses, the hypoxic fraction (pO2 < 5 mmHg, PO2 < 2.5 mmHg [p < 0.05]), the hemoglobin concentration (p < 0.05), and the hypoxic subvolume (p < 0.01) were of prognostic significance for overall survival. In multivariate analysis, the hemoglobin concentration and the hypoxic subvolume (p = 0.01) were significant prognosticators. We found no significant correlation between tumor volume or median pO2 and overall survival. No clear correlation was found between tumor volume and hypoxic fraction. CONCLUSION: These data suggest that the total amount of hypoxic tissue, as determined by the hypoxic subvolume, influences the prognosis of patients suffering from SCCHN. In addition, our data confirm the statements of previous studies that low pretherapy pO2-values indicate a worse prognosis.

High-dose radiation therapy alone for inoperable non-small cell lung cancer--experience with prolonged overall treatment times.

The purpose of this study as to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non-small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a restaging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n = 50), 12 weeks (n = 79) and > 12 weeks (n = 100), 5-year survival was 4%, 6%, and 8%, respectively (p = 0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment.

Is the time interval between surgery and radiotherapy important in operable nonsmall cell lung cancer? A retrospective analysis of 340 cases.

PURPOSE: To evaluate the influence of prognostic factors in postoperative radiotherapy of NSCLC with special emphasis on the time interval between surgery and start of radiotherapy. METHODS AND MATERIALS: Between January 1976 and December 1993, 340 cases were treated and retrospectively analyzed meeting the following criteria: complete follow-up; complete staging information including pathological confirmation of resection status; maximum interval between surgery (SX) and radiotherapy (RT) of 12 weeks (median 36 days, range 18 to 84 days); minimum dose of 50 Gy (R0), and maximum dose of 70 Gy (R2). Two hundred thirty patients (68%) had N2 disease; 228 patients were completely resected (R0). One hundred six (31%) had adenocarcinoma, 172 (51%) squamous cell carcinoma. RESULTS: In univariate analysis, Karnofsky performance status (90+ >60-80%; p = 0.019 log rank), resection status stratified for nodal disease (R+

[Combined breast-preserving surgery, chemotherapy and radiotherapy in the treatment of breast carcinoma. Effect of the interval between surgery and the beginning of radiotherapy]. / Kombinierte brusterhaltende Chirurgie, Chemotherapie und Strahlentherapie bei der Behandlung des Mammakarzinoms. Der Einfluss des Intervalls zwischen Operation und Bestrahlungsbeginn.

BACKGROUND: The timing of breast conserving surgery, chemotherapy, and radiotherapy in breast cancer treatment has become the subject of increasing interest over the last years. PATIENTS AND METHOD: Seventy-four patients who underwent postoperative radiotherapy at our institution between 1985 and 1992 form the basis of this study. Median follow-up time was 5 years. Seventy-three percent of patients were pre- or perimenopausal. Almost all patients (91%) were UICC-stage II. Axillary lymph nodes were positive in 95% of cases. Complete gross resection was achieved in all patients, and in 65% final pathological margins were free of invasive or intraductal carcinoma. Postoperatively, 70% of patients received 6 cycles of polychemotherapy (predominantly CMF) before onset of irradiation. The radiation dose was in almost all cases 60 Gy including 10 Gy boost. RESULTS: Five years after start of treatment overall survival, disease-free survival, and local recurrence rates were 86% (95%-confidence limits, 76 to 93%), 73% (61 to 83%), and 8% (3 to 16%), respectively. For disease-free survival, the only significant prognostic factor was the number of involved lymph nodes: 0 to 3 = 86%, > or = 4 = 40% (p < 0.0001). The interval between surgery and radiation (< or = versus > 20 weeks) had no significant influence on disease-free survival or local tumor control. In contrast, there was a trend of increased regional and distant failure with shortening of the interval due to the delivery of less than 6 cycles chemotherapy before the onset of radiotherapy. CONCLUSIONS: In our experience, there was no negative impact of a delay of radiotherapy in order to deliver full course chemotherapy before initiation of radiotherapy. However, the low statistical power of this analysis due to the small number of patients must be considered. it appears possible that a less intense chemotherapy before starting radiation treatment correlates with enhanced distant failure and subsequently decreased disease-free survival rates. Therefore, for patients at increased risk for distant metastasis, we prefer to give 6 cycles polychemotherapy before irradiation.

Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases.

PURPOSE: Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients with SCLC and SVCS as compared to SCLC without SVCS. METHODS AND MATERIALS: A retrospective analysis of 408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done. RESULTS: Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/- 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80-100%; p = 0.008) were of significant importance. CONCLUSIONS: SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended.

Prognostic factors in high-grade malignant glioma. A multivariate analysis of 76 cases with postoperative radiotherapy.

PURPOSE: Patients with malignant gliomas have a limited survival prognosis. We retrospectively analyzed data of malignant glioma patients with the aim of defining prognostic factors on which individualized treatment strategies might be built on. PATIENTS AND METHODS: Seventy-six patients with primary malignant glioma (51 glioblastoma multiforme, 20 anaplastic astrocytoma, 4 anaplastic oligo-astrocytoma, 1 anaplastic glioma) were postoperatively irradiated with 5 and 8 Me V photons, 2 Gy per fraction to a median total dose of 60 Gy (range 50 to 70 Gy). RESULTS: The youngest quartile of patients (up to 45 years) had the highest 3-year survival rates (mean +/- SE: 15 +/- 8%) and median survival time (17.9 months, 95% confidence interval: 9.2, 24.2 months) as compared to the oldest quartile (> 61 years) with no 3-year survivor and a median survival time of 9.7 months (7.2, 12.3 months). The middle quartiles (46 to 61 years) showed intermediate results. The difference between the youngest and oldest quartile (p = 0.01) and the middle quartile versus the oldest quartile (p = 0.04) was significant. In univariate analysis, tumor size (p = 0.04 for -30 mm vs > 50 mm) was of importance. In multivariate analysis only age of the patient reached statistical significance (p = 0.03). As compared to the youngest quartile of patients, the oldest quartile had a relative risk of 2.1 (95% confidence interval: 0.9, 5.1) of dying from the disease; the age group of 46 to 61 years had a relative risk of 2.0 (0.9, 4.3). CONCLUSIONS: Age of the patient is the most important factor for survival prognosis favouring younger age (< or = 45 years). The possible implications for radiation therapy are discussed.

Combined modality treatment of the rhabdomyosarcoma R1H of the rat: tumor and normal tissue response after cisplatin and conventional or accelerated irradiation treatment.

PURPOSE: To test the importance of the sequence of cisplatin and irradiation, either conventional or accelerated fractionated. METHODS AND MATERIALS: 30 fractions of 2 Gy were given in 6 or 3 weeks preceded or followed by (time interval between cisplatin and radiotherapy: 3 days) a single IP dose of 5 mg/kg cisplatin in the rhabdomyosarcoma R1H of the rat. Survival curves were generated, and comparisons were made by the log-rank test. RESULTS: After 60 Gy in 6 weeks, no local tumor controls were observed. If cisplatin was injected 3 days before start of 60 Gy/6 weeks, 11 +/- 10% (mean +/- SE) of the tumors were controlled. Cisplatin after radiotherapy resulted in 50 +/- 14% local controls. The difference was significant (p = 0.01) for cisplatin after radiotherapy in comparison to radiotherapy alone where no local controls were observed. After accelerated fractionation, 57 +/- 19% of the animals were cured with or without cisplatin before radiotherapy. If the drug was injected after end of 60 Gy/3 weeks, 86 +/- 13% survived recurrence free. The difference to accelerated radiotherapy alone was not significant. Accelerated radiotherapy produced significantly higher control rates than conventional radiotherapy (p < 0.001). CONCLUSIONS: Accelerated radiotherapy resulted in higher local tumor control rates as compared to conventional fractionated irradiation. Cisplatin combined with radiotherapy showed significantly better results if given after but not before irradiation, either conventional or accelerated fractionated.

Impact of tumor stroma on expression of the tumor bed effect in R1H rat rhabdomyosarcoma.

The impact of intratumoral stroma on the expression of the tumor bed effect was studied in R1H rat rhabdomyosarcoma. For this, either R1H tumors growing in subcutaneous tissues (in situ) were irradiated at median volumes of 40 mm3 with a single exposure of 15 Gy (200 kVp X rays), or fresh tumor fragments or cloned tumor cells cultured in vitro were transplanted into subcutaneous tissue 2 days after preirradiation with 15 Gy. The tumor bed effect was evaluated by the time necessary for experimental tumors to grow from 0.1 cm3 to 10 cm3. When irradiated in situ, R1H tumors expressed a clear-cut tumor bed effect. The growth rate was decreased by a factor of 1.8 +/- 0.2 compared to controls. A significant decrease in growth rate by a factor of 1.7 +/- 0.2 was also observed when cultured tumor cells were transplanted into preirradiated tissue. However, when tumor fragments were transplanted into preirradiated sites, no significant decrease in growth rate occurred in two independent experiments (1.0 +/- 0.1; 1.2 +/- 0.2). Our results indicate that vessels originating from the intratumoral stroma can modulate the expression of the tumor bed effect in R1H tumors.

[The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases]. / Strahlentherapie des inoperablen nichtkleinzelligen Bronchialkarzinoms. Eine retrospektive Analyse von 427 Fällen.

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.

Inoperable non-small cell lung cancer: a retrospective analysis of 427 patients treated with high-dose radiotherapy.

PURPOSE: The influence of patient and treatment characteristics on survival as well as normal tissue toxicity were retrospectively analyzed. METHODS AND MATERIALS: Four hundred twenty seven patients with unresectable non-small cell lung cancer received at least 60 Gy and two-thirds were treated with 70 Gy. RESULTS: Five-year survival rates and median survival time (95% confidence interval) were 2 +/- 2% (mean +/- s.e.) and 11.1 months (9.1-14.5) after 60-66 Gy (median 60 Gy); 8 +/- 2% and 14.9 months (13.3-16.5) after > or = 70 Gy (p = 0.0013). Stage I-II patients had significantly higher survival rates as compared to Stage III patients (p = 0.0015). Within the subgroup of Stage III patients those with Stage IIIA had significantly higher survival rates than Stage IIIB (p = 0.0167). Female patients achieved 5-year survival rates after 70 Gy of 15 +/- 7% as compared to only 7 +/- 2% of their male counterparts. Chemotherapy, histology, Karnofsky status, and age had no influence on survival after univariate and multivariate analysis. Nine percent and 11% of the patients suffered from moderate to severe pneumonitis and esophagitis. CONCLUSION: High-dose radiotherapy of unresectable non-small cell lung cancer with total doses > 60 Gy conventionally fractionated is feasible. With doses of > or = 70 Gy significantly higher survival rates were achieved as compared to 60-66 Gy. Normal tissue toxicity was acceptable. For Stage IIIB patients, however, treatment results are disappointingly low even after 70 Gy with no 5-year survivor.

Combined modality treatment of the rhabdomyosarcoma R1H of the rat: influence of sequence of cisplatin and fractionated irradiation.

The effect of irradiation with 30 fractions of 2 Gy in 6 weeks combined with a single dose of 5mg/kg cisplatin was studied in the rhabdomyosarcoma R1H of the rat and tumor response and normal tissue toxicity were assessed for various combinations of radiotherapy and chemotherapy. Cisplatin was given 3 days before, during (after the 5th and after the 10th fraction), or 3 and 17 days after radiotherapy. Five of the 12 tumors treated with cisplatin injected 3 days after radiotherapy were locally controlled (42%; 95% confidence intervals: 14-70%) as compared to 0/10 for radiotherapy alone (0%; 0-21%; p < 0.02). A similar trend was found for cisplatin injected 17 days after irradiation (2/6 local controls; 33%; 0-71%). With cisplatin given 3 days before radiotherapy 1/13 local controls were observed (8%; 0-22%; p < 0.05 when tested vs. cisplatin 3 days after radiotherapy). Tumor cure was dependent upon tumor size at time of cisplatin administration with 7/9 small tumors (< 2 mm3) cured versus only 2/35 cures of larger tumors (> 2 mm3). By contrast, net growth delay and skin damage were the same for combined modality treatment and for irradiation alone. General toxicity as assessed by body weight change was significantly higher for animals treated with cisplatin before or after radiotherapy, whereas cisplatin during radiotherapy showed equal effects as compared to radiotherapy alone. Although for the rhabdomyosarcoma R1H of the rat the combined modality treatment was shown to be more effective than radiotherapy alone when cisplatin was applied after radiotherapy, general toxicity was also higher for this mode of treatment.