Efficacy of whole brain radiotherapy combined with fractionated stereotactic radiotherapy in metastatic brain tumors, and prognostic factors

PURPOSE: We attempted to analyze the effectiveness of whole brain radiotherapy (WBRT) combined with fractionated stereotactic radiotherapy (FSRT) in brain metastases. METHODS: Thirty-seven metastatic brain tumors in 29 patients without previous treatment were treated with WBRT plus FSRT, from October 1996 to February 2002. Four of the patients received stereotactic radiosurgery (SRS) prior to WBRT. Non-small cell lung cancer was the most common type of primary tumor (20/29). The total dose to the whole brain ranged from 30 Gy to 40 Gy, and the boost dose from FSRT ranged from 12 Gy to 40 Gy. End points were survival rate and local control rates. Factors influencing survival were evaluated. RESULTS: Median survival was 13 months, and actuarial survival rates at one and two years were 81% and 39%, respectively. Actuarial one and two year local control rates for all lesions were 78% and 71%, respectively. Survival was significantly associated with age, tumor size, presence of active extracranial tumors, and performance status. No acute or delayed complications were observed. CONCLUSIONS: We believe that WBRT plus FSRT should be included in the treatment options for metastatic brain tumors, and we consider the effect of this non-invasive method to be quite good in patients with good prognostic factors, although other invasive modalities could also be effective in them.     

Brain metastasis from non-small cell lung cancer (NSCLC)

Background and purpose

This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC).

Material and methods

A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5?×?4 Gy or 10?×?3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung?+?bone vs. lung?+?lymph nodes vs. other combinations) extracranial organs.

Results

The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥?4 extracranial organs were 52, 27, 17, 4, and 14?%, respectively (p?<?0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95?% confidence interval 1.19–1.46; p?<?0.001). Age <?65 years (p?=?0.004), KPS ≥?70 (p?<?0.001), and only 1–3 brain metastases (p?=?0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement.

Conclusion

The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement.     

A New Scoring System to Predicting the Survival of Patients Treated with Whole-Brain Radiotherapy for Brain Metastases

PURPOSE: To create a scoring system to estimate survival of patients who received whole-brain radiotherapy (WBRT) for brain metastases. MATERIAL AND METHODS: Based on a multivariate analysis of 1,085 retrospectively analyzed patients, a scoring system was developed. This score was based on the four significant prognostic factors found in the multivariate analysis including: age, performance status, extracranial metastases at the time of WBRT, and interval between tumor diagnosis and WBRT. The score for each prognostic factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the partial scores for each prognostic factor. Total scores ranged from 9 to 18 points, and patients were divided into four groups. For each group, survival was compared for short-course (5 x 4 Gy) versus longer-course WBRT (10 x 3 Gy/20 x 2 Gy). RESULTS: Actuarial 6-month survival rates were 6% for patients with scores of 9-10 points, 15% for those with scores of 11-13 points, 43% for those with scores of 14-16 points, and 76% for those with scores of 17-18 points (p < 0.001). Longer-course WBRT was not associated with better survival than short-course WBRT in any of the four groups. CONCLUSION: Patients with brain metastases receiving WBRT can be grouped with this score to estimate survival. Short-course and longer-course WBRT resulted in similar survival in all groups studied. However, in the more favorable patients with scores of 17-18, longer-course WBRT with lower doses per fraction should be considered, as these schedules have been associated with less neurocognitive toxicity.     

Comparison of Short-Course versus Long-Course Whole-Brain Radiotherapy in the Treatment of Brain Metastases

BACKGROUND AND PURPOSE: Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases. Most of these patients have a poor survival prognosis. Therefore, a short radiation program is preferred, if it provides a similar outcome as longer programs. This study compares 20 Gy in five fractions (treatment time: 1 week) to longer programs, with higher doses including 30 Gy in ten fractions (2 weeks) and 40 Gy in 20 fractions (4 weeks). PATIENTS AND METHODS: Data regarding 1,085 patients treated with WBRT for brain metastases were retrospectively analyzed. 387 patients received 20 Gy in five fractions, and 698 patients received higher doses (30 Gy in ten fractions, n = 527, or 40 Gy in 20 fractions, n = 171). In addition, eight potential prognostic factors were investigated including age, sex, Karnofsky Performance Score (KPS), tumor type, interval from tumor diagnosis to WBRT, number of brain metastases, extracranial metastases, and recursive partitioning analysis (RPA) class. Subgroup analyses were performed for each RPA class individually. RESULTS: The WBRT schedule had no significant impact on survival (p = 0.415). On multivariate analysis, improved survival was significantly associated with age < or = 60 years (risk ratio [RR]: 1.28; p < 0.001), KPS > or = 70 (RR: 1.73; p = 0.002), lack of extracranial metastases (RR: 1.27; p = 0.007), interval from tumor diagnosis to WBRT > 8 months (RR: 1.19; p = 0.011), and lower RPA class (RR: 1.56; p < 0.001). The subgroup analyses for each RPA class did not reveal a significant association between WBRT schedule and survival. CONCLUSION: Short-course WBRT with 20 Gy in five fractions is preferable for most patients, because it is associated with similar survival as longer programs and is less time-consuming.     

Whole-Brain Radiotherapy with 20 Gy in 5 Fractions for Brain Metastases in Patients with Cancer of Unknown Primary (CUP)

BACKGROUND: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. PATIENTS AND METHODS: Data regarding 101 CUP patients who received either short course WBRT (n=34) with 5 x 4 Gy or long-course WBRT (n=67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. RESULTS: On univariate analysis, the radiation program was not associated with survival (p=0.88) nor intracerebral control (p=0.36). Improved survival was associated with KPS >or= 70 (p<0.001), absence of extracranial metastases (p<0.001), and RPA-class 1 (p<0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p<0.001), extracranial metastases (RR: 1.70; p=0.018), and RPA-class (RR: 2.86; p<0.001) maintained significance. On univariate analysis, KPS (p<0.001) and RPA-class (p<0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p<0.001) and RPA-class (RR: 2.09; p<0.001) remained significant. CONCLUSION: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients.     

Treatment of Cerebral Metastases from Breast Cancer with Stereotactic Radiosurgery

BACKGROUND AND PURPOSE: The role of stereotactic radiosurgery (SRS) alone or in combination with whole brain radiotherapy (WBRT) in the treatment of cerebral metastases from breast carcinoma is discussed controversially. To elucidate the role of SRS in this context, a retrospective study evaluating the benefit of SRS and prognostic factors for survival was performed. PATIENTS AND METHODS: From 1986 to 2003, 62 patients with cerebral metastases from breast cancer were treated for 103 lesions. Ten patients received SRS alone (group 1), 13 patients were treated with WBRT and SRS as a focal boost (group 2), and 39 patients received WBRT and salvage SRS (group 3) for recurrent metastases at a later time point. RESULTS: Survival was increased in patients receiving SRS only compared to WBRT and SRS as a focal boost. Patients < 40 years of age had a favorable outcome (p > 0.04). However, no other prognostic factors could be identified. Overall tolerance of radiation was acceptable. Median local control intervals were 9 months for all patients, 6.5 months in group 1, 4 months in group 2, and 9 months in group 3, respectively. There were no significant intergroup differences. CONCLUSION: SRS alone is an effective treatment for patients with one to three brain metastases from breast cancer. A randomized trial should be performed to evaluate whether WBRT is a necessary component in the primary treatment of these patients. Salvage SRS is an effective therapy option after WBRT.     

Linac Radiosurgery Versus Whole Brain Radiotherapy for Brain Metastases

BACKGROUND AND PURPOSE: For patients with inoperable brain metastases, whole brain radiotherapy (WBRT) has been the standard treatment for decades. Radiosurgery is an effective alternative strategy, but has failed to show a substantial survival benefit so far. The prognostic factors derived from the RTOG recursive partitioning analysis (RPA) provide a framework that allows a nonrandomized comparison of the two modalities. PATIENTS AND METHODS: From 1991 to 1998, 117 patients with one to three previously untreated cerebral metastases underwent single-dose linac radiosurgery (median dose 20 Gy) without adjuvant WBRT. After radiosurgery, 26/117 patients (22%) had salvage WBRT, radiosurgery or neurosurgical resection of recurrent (4/117) and/or new (24/117) metastases. Survival of these patients was compared to a historical group of 138 patients with one to three lesions treated by WBRT (30-36 Gy/3-Gy fractions) from 1978 to 1991; only nine of these patients (7%) had salvage WBRT. All patients were classified into the three RPA prognostic classes based on age, performance score, and presence of extracranial tumor manifestations. RESULTS: In RPA class I (Karnofsky performance score > or = 70, primary tumor controlled, no other metastases, age < 65 years), radiosurgery resulted in a median survival of 25.4 months (n = 23, confidence interval [CI] 5.8-45.0) which was significantly longer than for WBRT (n = 9, 4.7 months, CI 3.8-5.5; p < 0.0001). In RPA class III (Karnofsky performance score < 70), no significant difference in survival between radiosurgery (n = 20, 4.2 months, CI 3.2-5.3) and WBRT (n = 68, 2.5 months, CI 2.2-2.8) was found. In RPA class II (all other patients), radiosurgery produced a small, but significant survival advantage (radiosurgery: n = 74, 5.9 months, CI 3.2-8.5, WBRT: n = 61, 4.1 months, CI 3.4-4.9; p < 0.04). CONCLUSION: Radiosurgery in patients with one to three cerebral metastases results in a substantial survival benefit only in younger patients with a low systemic tumor burden when compared to WBRT alone. It cannot be excluded that this effect is partially caused by the available salvage options after radiosurgery.     

伽玛刀立体定向放疗结合全脑照射治疗脑转移瘤临床效果分析

目的 分析立体定向放疗结合全脑照射治疗脑转移瘤的疗效和预后,同时观察服用替莫唑胺(TMZ)与放疗结合对患者生存率的影响。方法 脑转移瘤患者52例,按照治疗方法不同分为2组,一组为全脑照射(WBRT)+立体定向放疗(SRT,伽玛刀),共35例,一组为单纯SRT,共17例。全脑放疗分次剂量为1.8~3.0 Gy/次,1 次/d,5 次/周,总剂量D_T30~40 Gy,WBRT+SRT组全脑后伽玛刀补量采用45%~75%等剂量曲线包绕PTV,边缘剂量12~15 Gy,中心剂量20~30 Gy。单纯SRT组分次立体定向放疗采用45%~75%等剂量曲线包绕PTV,边缘剂量36~40 Gy,中心剂量70~80 Gy。随访1~2年。所选52例患者中有20例患者放疗期间及放疗后服用替莫唑胺胶囊,同步化疗组化疗方案为:口服替莫唑胺75 mg/m²,1次/d,直至放疗结束,放疗结束后再服用3~6个月,剂量改为150 mg/m²。结果 放射治疗后1~3个月,复查CT/MRI显示总有效率(CR+PR)为84.62%,WBRT+SRT组有效率为88.57%,SRT组有效率为76.47%;肿瘤的6个月及1年的局部控制率分别为92.10%和85.20%。WBRT+SRT组的平均生存期13.2个月,中位生存期11个月;6个月生存率为71.40%,12个月生存率为54.30%,18个月生存率为14.30%。SRT组的平均生存期10.2个月,中位生存期9个月;6个月生存率为41.20%,12个月生存率为23.50%,18个月生存率为5.88%。替莫唑胺+放疗与单纯放疗的6个月、12个月及18个月生存率分别为80.00%和56.30%、60.00%和37.50%、10.00%和12.50%。结论 WBRT+SRT治疗脑转移瘤总体上优于单纯SRT治疗。放疗+TMZ联合治疗与单纯放疗相比,替莫唑胺在放疗过程中服用可提高患者生存率,不良反应无显著增加。     

The Role of Postoperative Radiotherapy after Resection of a Single Brain Metastasis

BACKGROUND AND PURPOSE: The extent of treatment in patients with single brain metastasis is a controversial topic. Especially the issue of whole-brain radiotherapy (WBRT) after local treatment of the lesion is largely unresolved. Therefore, the authors performed a pooled analysis of all available clinical data, based on a comprehensive literature search and on prospectively defined inclusion criteria and endpoints (in particular local brain control at the original site and development of new brain metastases). MATERIAL AND METHODS: Overall, 643 patients from ten publications met the inclusion criteria. 106 patients were treated with surgery alone, 66 with surgery plus local radiotherapy, and the others with surgery plus WBRT (Table 1). RESULTS: Both types of additional radiotherapy significantly improved local control at the original site (relative risk of local failure <0.5). WBRT also reduced new lesions significantly (relative risk 0.6). Within the available range of doses, no significant dose-response relationship was observed (Figure 1). Even after WBRT, new lesions remained the predominant type of brain failure. One of the underlying causes might be continuous reseeding of cells from active extracranial sites. Toxicity and quality of life were not well described in the publications. CONCLUSION: The present data favor moderate-dose WBRT, but the pros and cons of each option should be discussed with each patient. Higher radiation doses or local boost treatment are not supported by these data, but might be considered under certain circumstances, e.g., after incomplete resection.     

Early mammographic and sonographic findings after intraoperative radiotherapy (IORT) as a boost in patients with breast cancer

The aim of this study was to evaluate mammographic and sonographic changes at the surgical site within the first 2 years after IORT as a boost followed by whole-breast radiotherapy (WBRT), compared with a control group treated with WBRT alone. All patients had breast-conserving surgery for early-stage breast cancer. Group A: n = 27, IORT (20 Gy) followed by WBRT (46 Gy). Group B (control group): n = 27, WBRT alone (56-66 Gy). Mammography: fat necrosis in 14 group A versus four group B patients (P < 0.001); parenchymal scarring classified as unorganized at the last follow-up in 16 vs seven cases, respectively (P = 0.03). Ultrasound: overall number of patients with circumscribed findings 27 vs 18 (P < 0.001); particular hematomas/seromas in 26 vs 13 patients (P < 0.001). Synopsis of mammography and ultrasound: overall postoperative changes were significantly higher classified in group A (P = 0.01), but not judged to have a significantly higher impact on interpretation. Additional diagnostic procedures, due to unclear findings at the surgical site, were performed on four patients of both groups. Within the first 2 years after IORT as a boost, therapy-induced changes at the original tumor site are significantly more pronounced compared with a control group. There is no evidence that the interpretation of findings is complicated after IORT.     

Die kombinierte Behandlung des lokal begrenzten Prostatakarzinoms mit HDR-Iridium-192-Nachlade-Brachytherapie und perkutaner Bestrahlung

BACKGROUND: The localized prostate cancer can be treated curatively by radiation therapy. The combined treatment of external beam irradiation and HDR-Iridium 192 remote brachytherapy allows higher radiation doses within the tumor without increasing radiation sequelae. PATIENTS AND METHODS: Patients of our clinic have been treated with this combined procedure since 1991. Between 1991 and 1994 15 patients received 2 x 9 Gy of high-dose-rate brachytherapy, followed by 36 Gy external beam irradiation (group A). Because of the frequent local failures in group A, the reference dose of external beam irradiation was increased to 50.4 Gy after brachytherapy between 1994 and 1996. RESULTS: Seven of 15 patients (47%) in group A developed a local recurrence after a median of 17 (13 to 30) months. In group B (20 patients) local failure occurred in 3 patients (15%) after 11, 16 and 32 months. CONCLUSION: The combined radiation therapy of localized prostate cancer cannot substitute radical prostatectomy completely, but it is a promising alternative in the curative treatment in selected patients.     

Die rolle der strahlentherapie in der behandlung maligner meningiome

PURPOSE: Most malignant meningiomas will recur following surgical resection only. The role of irradiation and radiation dose levels is poorly defined. This study reviews a single institution experience using both, conventional and high doses > or = 60 Gy/CGE radiation regimen. PATIENTS AND METHODS: Between 1974 and 1995 16 patients with histologically proven malignant meningioma underwent radiation therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years). Three patients reported previous irradiation to the head at least 14 years prior to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent disease. Six patients underwent gross total and 10 patients subtotal resection (Table 1). RT was delivered using conventional, megavoltage photons or combined 160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent) (median: 58 Gy/CGE, Table 2). RESULTS: With median observation time of 59 months (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were 52% and 17%, respectively. Target doses > or = Gy/CGE resulted in significantly improved tumor control (100%) compared to < 60 Gy/CGE (17%) (p = 0.0006, Table 3 and Figure 1). Improved local control translated also in increased overall survival: 87% (> or = 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025, Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. CONCLUSION: Conformal, radiation therapy with target doses > or = 60 Gy/CGE, in this study by use of combined proton and photon irradiation, can significantly improve chances of long-term local control and survival for patients diagnosed with these challenging tumors.     

Brain metastasis

Background and purpose

This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis.

Material and methods

The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs.

Results

The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥?4 extracranial organs were 51, 30, 16, 13, and 10?%, respectively (p?<?0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95?% confidence interval 1.18–1.34; p?<?0.001). According to the multivariate analysis, age (p?<?0.001), gender (p?=?0.002), and KPS (p?<?0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved.

Conclusion

The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.     

Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

BACKGROUND AND PURPOSE: Topotecan penetrates the blood-brain barrier and sensitizes tumor cells against radiation. A phase I/II dose-escalating trial of repetitive daily i. v. topotecan application simultaneously with whole-brain irradiation (WBRT) was conducted to estimate toxicity, maximum tolerated dose and survival in patients with inoperable brain metastases. PATIENTS AND METHODS: In 47 patients suffering from previously untreated brain metastases, topotecan was applied on a daily i. v. schedule simultaneously with WBRT (36 Gy/3-Gy fractions). The infusion schedule started at the beginning of WBRT and was discontinued during weekends. Each infusion was completed within 1-2 h before irradiation. In a dose-finding study, topotecan was escalated from 5 x 0.5 mg/m(2), 8 x 0.5 mg/m(2), 12 x 0.5 mg/m(2) to 12 x 0.6 mg/m(2). RESULTS: Altogether, 38/47 patients (81%) completed the prescribed schedule. Leukopenia and thrombocytopenia were dose-limiting. Grade 3/4 hematologic toxicity occurred in 5/32 chemona?ve patients (16%) and 7/15 patients (47%) with previous chemotherapy. At 12 x 0.6 mg/m(2), 2/4 patients experienced grade 4 leukopenia/thrombopenia. Nonhematologic toxicities were generally mild to moderate and unrelated to topotecan. Response evaluation was possible in 26/47 patients, overall response rate was 58% (CR [complete remission] 5/26, PR [partial remission] 10/26, NC [no change] 8/26). Median survival amounted to 5.1 months. In 15/42 patients (36%), brain metastases were the dominant cause of death. CONCLUSION: For a daily topotecan schedule simultaneous to WBRT, the maximum tolerated dose is 12 x 0.5 mg/m(2) in chemona?ve patients. For chemo-pretreated patients, daily doses should be reduced to 0.4 mg/m(2). A phase III trial has now been started to find out whether WBRT + topotecan increases survival compared to WBRT alone.     

肺癌脑转移44例治疗分析

目的比较不同治疗方法对肺癌脑转移的疗效。方法对44例肺癌脑转移患者资料进行回顾性分析。根据治疗方法的不同分为单纯放疗组23例(全脑放疗10例,立体定向放疗13例),全脑放疗或立体定向放疗联合全身化疗(放疗+化疗)组17例,对症治疗组4例,比较其生存期和生存率。结果 单纯放疗组的中位生存期为8.3个月,1年生存率为17.4%;放疗+化疗组中位生存期为13.2个月,1年生存率为52.9%;对症治疗组的中位生存期为1.7个月,1年生存率为0%。放疗+化疗组比单纯放疗及对症治疗组具有更好的疗效(P<0.05)。结论放疗联合化疗是肺癌脑转移患者比较有效的治疗方法,可延长生存期。     

Long-Term Survival Following Radiotherapy and Cytarabine Chemotherapy for Sporadic Primary Central Nervous System Lymphoma

PURPOSE: To analyze the long-term results following whole brain radiotherapy (WBRT) with sequential intrathecal (i.th.) cytosine arabinoside (Ara-C) +/- intravenous (i.v.) Ara-C in patients with primary central nervous system lymphoma (PCNSL). PATIENTS AND METHODS: 14 patients were treated between July 1987 and August 1995. All had sporadic PCNSL with proven histology of high-grade CNS lymphoma (twelve diffuse large-cell B-lymphomas, one lymphoblastic lymphoma, one large T-cell lymphoma). Patients were treated with two to four cycles of induction chemotherapy (40 mg/m2 Ara-C i.th.), four patients received additional Ara-C i.v. (150 mg/m2, d1-4). WBRT was administered using 1.8-Gy fractions. Intrathecal chemotherapy was planned afterwards in 4-week intervals for 6 months. Posttreatment neurocognitive evaluations were performed in two long-term survivors. RESULTS: Two of four patients who received i.v. and i.th. induction chemotherapy showed progressive disease, and irradiation was started immediately. Six of 14 patients received 50.4 Gy WBRT, four patients had WBRT up to 39.6 Gy followed by a 10.8-Gy boost. Five patients died early during therapy either due to a decline of the general medical condition or progressive disease. Median survival was 41 months (95% confidence interval: 6-79 months), survival at 3 and 5 years was 59% and 42%, respectively. Six patients survived for 3 years, two younger patients are still alive (> 12 years). They show only slightly impaired neurocognitive functions without clinical relevance. CONCLUSION: This WBRT-based protocol with i.th. meningeal prophylaxis using Ara-C +/- i.v. Ara-C yields substantial long-term survival with moderate toxicity. The value of i.v. chemotherapy is currently being investigated in prospective studies.     

替加氟同步放疗治疗消化道肿瘤脑转移效果观察

 目的 观察替加氟同步放疗治疗消化道肿瘤脑转移的疗效及不良反应。方法 将43例消化道肿瘤脑转移患者随机分为观察组和对照组,对照组采用全脑普照30 Gy后,局部补量至50 Gy,观察组在静脉滴注替加氟1.0 g后30 min以上行放疗,通过随访及定期MRI检查观察生存时间、脑部转移灶复发率、原发病灶复发、未控和（或）非脑部器官转移率、半年及1年生存率和不良反应的发生率等指标的变化。结果 观察组及对照组中位生存期分别为13、9个月（χ²=10.282,P=0.001）;1年生存率分别为53.4%、27.3%（χ²=6.85,P=0.009）;脑部转移灶复发率分别为9.5%、45.5%（χ²=5.22,P＜0.05）;骨髓抑制发生率分别为85.7%、40.9%（χ²=7.41,P＜0.05）;消化道反应发生率分别为61.9%、10%（χ²=10.97,P＜0.05）,两组比较,差异均有统计学意义。结论 替加氟同步放疗能够提高消化道肿瘤脑转移患者的1年生存率,降低脑部转移灶的发生率;替加氟同步放疗增加了患者的骨髓抑制和消化道反应发生率,但经对症处理后均能缓解。     

Multimodal treatment of locally advanced carcinoma of the breast. Experience at the Galliera di Genova Hospital

All patients with locally advanced breast cancer receiving definitive irradiation (with or without surgery) at the Radiation Oncology Service, Ospedali Galliera, Genova, Italy, from 1969 through 1986, were retrospectively reviewed. Group A consisted of 187 patients, affected with stage III disease, who received radiation therapy after radical surgery. Irradiation of the chest wall and regional lymph node chains was accomplished with divergent tangential beams of Cobalt: the dose was calculated at the mid-plane of the tangential field separation and was 50Gy (2 Gy/day, 5 fractions/week), followed by additional 10-15 Gy boost to the scar. One hundred and five patients received combined hormonotherapy and/or chemotherapy. After a mean follow-up of 49+ months we observed 21 local recurrences (16 in metastatic patients); 64 patients developed only distant metastases. Actuarial survival at 5 years is 55%. Group B consisted of 36 inoperable patients who received definitive irradiation. Radiation therapy planning was very similar to that in group A, even though after 50 Gy the breast and the tumor area were boosted with restricted fields up to a total dose of 80-90 Gy. Fifteen patients received combined hormonotherapy and/or chemotherapy. At the end of the treatment overall response rate was 89%; actuarial survival at 5 years is 38%. Toxicity was generally mild and no death related to the treatment was observed. Our retrospective analysis confirms the importance of a multimodal approach to locally advanced breast cancer in order to free most patients from disease and to produce excellent local control, even though more randomized studies are necessary to improve the long-term survival of these patients.     

Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract.

AIM: To assess effect and toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. PATIENTS AND METHODS: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. RESULTS: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter < 20 mm, the lack of radiological mediastinal involvement, a complete remission, and a Karnofsky performance status > 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grade-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in group A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). CONCLUSIONS: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients.