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.     

Results of combined-modality therapy for primary and secondary malignant lymphoma of the central nervous system (CNS)

PURPOSE: We consider that whatever the vital prognosis of secondary CNS lymphoma (SCNSL), its local control is as serious as that of primary CNS lymphoma (PCNSL). In this study, both the treatment outcomes and local control of patients with SCNSL and PCNSL were compared, with the aim of improving the treatment of SCNSL. MATERIALS AND METHODS: This study included 11 patients with PCNSL and 14 with SCNSL treated from January 1984 to October 1997. PCNSL patients underwent partial tumor resection and received systemic chemotherapy. All SCNSL patients received systemic chemotherapy, and eight also received intrathecal anticancer drug infusion. Nine PCNSL patients and 11 SCNSL patients underwent whole-brain radiation therapy with 4-MV photons. Among the SCNSL patients, three patients underwent localized-brain irradiation and two patients also received whole-spine irradiation. RESULTS: Five-year survival rates were 34% for PCNSL and 33% for SCNSL. In SCNSL, survival times after CNS involvement were very short, irrespective of treatment. One-year local control rates after CNS irradiation were 38% for PCNSL and 14% for SCNSL. Recurrence was mainly found in the cranial region, in seven of 11 PCNSL patients and 10 of 14 SCNSL patients. CONCLUSIONS: Patients with SCNSL had a poor prognosis, and local control in them was more problematic than in patients with PCNSL. It is necessary to develop new combined modality therapy for patients with SCNSL,including the participation of a radiation oncologist, before the disease becomes progressive.     

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。     

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.     

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.     

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

BACKGROUND AND PURPOSE: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. PATIENTS AND METHODS: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). RESULTS: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. CONCLUSION: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.     

Radiotherapy in the combined therapy of limited stage pulmonary microcytoma. The experience of the Department of Oncologic Therapy at the Multiregional Hospital of Varese (1980-1989)]

From January 1980 to December 1989, 86 patients with limited small cell lung carcinoma (SCLC) were treated in our Institution. Sixty-eight of them were males, 18 females; mean age was 58 years (range: 40-74); Karnofsky index was 80 or higher. All patients received induction multiagent chemotherapy (CAV or CAVE), usually fractionated into 3/4 cycles. Radiotherapy was administered by means of a 10 MV Linear Accelerator, 2-3 Gy/day, 5 days/week. Radiation dose was 60 Gy for 39 patients, 50 Gy for 25 patients, and 30 Gy for 22 patients. Parallel opposed fields (AP and PA) were used for administering the 30-Gy dose, while higher doses were delivered by multiportal arrangement (3/4 fields). Overall survival (corrected Kaplan-Meier) was 21.3% and 13.4% at 2 and 3 years, respectively; 2 years' survival according to dose was 24.5% for 60 Gy, 19.9% and 11% for 50 and 30 Gy, respectively. Mean survival time (MST) was 14 months for 60 Gy, 13 months and 10 months, respectively, for 50 and 30 Gy. Survival and disease-free survival rates were similar in patients who received 50 and 60 Gy. No major complications related to irradiation were observed, not even in the group receiving the highest dose. Our data are similar to those reported in the literature.     

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.     

Radiotherapy for Orbital Lymphoma

PURPOSE: To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: 42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II-IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20-46 Gy) for indolent lymphoma and 44 Gy (20-48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy. RESULTS: The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness). CONCLUSION: Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.     

Chemo-radiotherapy in advanced head and neck tumors. Personal experience]

From January 1981 through December 1983, 49 untreated patients with locally advanced head and neck cancers were randomized in two groups to receive different radiochemotherapy regimens. Group A, including 29 cases, received 4 cycles of induction chemotherapy with Bleomycin, Methotrexate and Hydroxyurea before definitive external radiotherapy (60 Gy); group B, including 20 patients, received the same total dose of radiotherapy but the 4 cycles of chemotherapy, as described above, were administered between the 20- and the 40-Gy doses. Both groups were compared with a control group treated in the same period with radiotherapy (60 Gy) alone. The response to treatment was evaluated at the end of chemotherapy or radiotherapy alone and at the end of combined regimens. Long-term survival rates were analyzed for all groups relative to complete tumor response, disease-free interval and time to disease progression. In our experience the radio-chemotherapy combination, according to the described schedules, failed to improve both local control and overall survival; the comparison with the control group does not suggest that induction or intercalated chemotherapy can increase long-term survival even if initial complete and partial response rates are high.     

Treatment of Solitary Brain Metastasis

BACKGROUND: Whole brain radiation therapy (WBRT) is reported to improve local control after resection of brain metastases. Improvement of survival was only observed in patients with controlled extracranial disease. The optimum radiation schedule has yet to be defined. The authors' experience with a postoperative approach including WBRT and a radiation boost to the metastatic site is presented. PATIENTS AND METHODS: Criteria for inclusion into this retrospective analysis were solitary brain metastasis, Karnofsky performance status > or = 70%, and controlled extracranial disease. Two therapies were compared for local control and survival: surgery followed by 40 Gy WBRT (group A) versus surgery followed by 40 Gy WBRT and a 10 Gy boost (group B). Statistical analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: 33 patients were included (17 group A, 16 group B). The results suggested better local control (p = 0.0087) and survival (p = 0.0023) for group B. 17/17 patients (100%) of group A and 13/16 patients (81%) of group B showed progression of brain metastasis, 8/17 and 3/16 patients in the area of metastatic surgery. Median time to progression was 7 (1-22) months in group A and 12 (3-42) months in group B. The number of cancer-related deaths amounted to 17/17 (100%) in group A after a median interval of 9 (3-26) months, and to 9/16 (56%) in group B after 14 (4-46) months. CONCLUSION: After resection of solitary brain metastasis, a radiation boost in addition to WBRT seems to improve local control and survival when compared to postoperative WBRT alone. The results should be confirmed in a larger prospective trial.     

Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital experience

A retrospective review was conducted of patients treated for thyroid non-Hodgkin's lymphoma (TNHL) at the Royal Marsden Hospital between 1936 and 1996 to determine the effect of radiotherapy (RT) on outcome. 91 patients were identified from the Thyroid Unit Database. There were 77 females and 14 males with a median age of 65 years (range 22-87 years). RT was delivered according to two separate policies: (1) involved field radiotherapy (IFRT) to the thyroid bed and cervical lymph nodes; (2) extended field radiotherapy (EFRT) covering the thyroid bed, cervical and mediastinal lymph nodes. 89 patients received RT as part of definitive treatment following surgery, to a dose of approximately 40 Gy. 25 patients received IFRT and 64 patients EFRT. 27 patients received cytotoxic chemotherapy. 18 patients (72%) treated with IFRT died of TNHL with a median relapse free survival (RFS) of 10 months and a median overall survival (OS) of 21 months. In contrast, only 29 patients (46%) treated with EFRT died of TNHL with a median RFS of 76 months (p = 0.01 for RFS with respect to IFRT and p = 0.04 for OS). Significantly more patients treated with IFRT relapsed locally (52% vs 27%). There was no difference in the rates of systemic relapse (20% vs 22%). EFRT alone for Stage I, but not for Stage II disease, yielded acceptable rates of local control and disease free survival with doses of at least 40 Gy. These historical data strongly support the addition of combination chemotherapy to the treatment regimen in all patients with Stage II disease. Indeed, in recent years this has become the standard of care for all cases of thyroid lymphoma unless the histology is of marginal zone type (mucosa associated lymphoma tissue (MALT) lymphoma).     

Mitomycin C, 5-fluorouracil and radiation in advanced, locally recurrent rectal cancer.

15 patients with inoperable presacral recurrent rectal cancer following surgery were treated with combined radiation and chemotherapy. Treatment consisted of split-course radiotherapy with 50 Gy in 25 fractions over 5 weeks and, after 4 weeks, an additional 20 Gy in 10 fractions over 2 weeks. At the start of treatment and following the split course, chemotherapy was administered. Mitomycin C was given on Day 1 (dose: 15 mg/m2 i.v. bolus) and 5-fluorouracil from Day 1 to Day 5 (dose: 750 mg/m2/24 h, continuous i.v. infusion). Owing to considerable, predominantly haematological and gastrointestinal toxicity, only six out of 15 patients received treatment according to the protocol. The symptomatic relief of symptoms was good. Pain was controlled in seven of eight symptomatic patients. Seven of the patients showed response according to computed tomography, but in none of these cases was a complete remission seen. After a follow-up of at least 30 months, only three patients are alive. The 1-, 2- and 3-year survival rates are 9/15, 6/15 and 3/12, respectively. The median survival is 14 months (range 4-60+ months). In comparison with historical data from the same institution, combined radio-chemotherapy did not show any prolongation of survival or increased response rate, but increased toxicity excessively, when compared with radiation alone.     

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.     

Intracranial germinoma: radiation therapy with tumor volume-based dose selection

PURPOSE: To prospectively investigate whether intracranial germinomas, except large ones, can be cured with radiation doses lower than 50 Gy and to determine 10-year follow-up results. MATERIALS AND METHODS: Between 1985 and 1995, 38 patients with intracranial germinoma diagnosed histologically or with established criteria were enrolled. Total radiation doses to the primary tumor site were 36 Gy after total removal, 40 Gy for tumors less than 2.5 cm in diameter, 45 Gy for those 2.5-4.0 cm, and 50 Gy for those greater than 4.0 cm, with 1.6-1.8-Gy daily fractions. Patients underwent irradiation of the primary tumor site or cerebrospinal axis (20-24 Gy), depending on findings at diagnosis. No chemotherapy was allowed. RESULTS: All patients completed radiation therapy. Thirty-five patients were treated according to protocol, and three with relatively slow tumor regression or presence of a cyst received additional radiation (5-7 Gy, 50-52 Gy total). Ten-year overall and relapse-free survival rates were 91% and 95%, respectively. Two patients developed meningeal dissemination, but none had local failure. Treatment complications included chordoma in one patient and internal carotid artery occlusion in another. No treatment-related decline of performance status was observed in the other patients. CONCLUSION: All tumor volume-based radiation doses were effective, without risk of local failure. Intracranial germinoma 4 cm or less in diameter can be cured with doses of 40-45 Gy. Investigation of further dose reduction seems worthwhile. Radiation therapy alone with these doses should be compared with ongoing chemotherapeutic protocols plus low-dose (24-30-Gy) irradiation in future studies.     

Concurrent Radiochemotherapy with Vinorelbine plus Cisplatin or Carboplatin in Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC) and an Increased Risk of Treatment Complications

BACKGROUND: In elderly patients, patients with multiple morbidities, and patients with a reduced general condition, the standard treatment of inoperable non-small-cell lung cancer (NSCLC) consists of either chemotherapy or radiation therapy alone and is associated with an extremely poor prognosis. We therefore investigated the feasibility, toxicity, and efficacy of radiotherapy with concurrent chemotherapy using vinorelbine plus cisplatin or carboplatin in NSCLC patients at risk for treatment complications. PATIENTS AND METHODS: A total of 33 patients (six women, 27 men, median age 65 years) with locally advanced, functionally inoperable pulmonary carcinomas, recurrent lung cancer or postoperative macroscopic residual tumors (R2) with an increased risk of treatment complications (WHO performance status 2/3; cardiac, renal or pulmonary failure; marked pretherapeutic weight loss; age between 71-75 years) received 12.5 mg of vinorelbine per m(2) body surface area (BSA) on days 1, 8, 15, 29, 36 and 43 plus either cisplatin 20 mg/m(2) BSA (ten patients) or carboplatin 70 mg/m(2) BSA (23 patients) on days 1-5 and 29-33 together with conventionally fractionated radiotherapy. The tumor regions were irradiated with doses of up to 63 Gy (90% isodose), and potentially affected lymph nodes received doses of up to 45.0 or 50.4 Gy (90% isodose). RESULTS: Briefly, 31 of 33 patients successfully completed radiation therapy and 26 received four cycles of vinorelbine plus at least two cycles of cisplatin or carboplatin. Hematotoxic side effects included grade III leukocytopenia (n = 8), grade III thrombocytopenia (n = 5), and grade IV thrombocytopenia (n = 2). Other side effects consisted of peripheral neuropathy grade III (n = 1) and esophagitis grade IV (n = 1). Severe pneumonitis did not occur. Six patients had pneumonia before radiochemotherapy. 21 patients (63%) exhibited a complete (n = 7) or partial response (n = 14) to chemoradiation. The twelve nonresponders had either stable (n = 9) or progressive disease (n = 3). The survival rates plus standard deviations were as follows: 1-year survival: 60 +/- 8%, 2-year survival: 36 +/- 9%, 3-year survival: 24 +/- 9%, median survival time: 17 months (5;29 months; 95% confidence interval [CI]), median progression-free survival: 11 months (9;13 months; 95% CI). The median follow-up time was 14 months. CONCLUSION: Conventionally fractionated radiochemotherapy with vinorelbine plus a platinum derivative is feasible in patients with NSCLC and increased risk of treatment complications. Compared to patient populations described in the literature, the survival rates achieved by concurrent radiochemotherapy appear to be better than those achieved with radiotherapy alone.     

Radiotherapy for Stage I–III Nodal Low-Grade Non-Hodgkin’s Lymphoma

BACKGROUND: To evaluate retrospectively long-term results and patterns of recurrence in patients with low-grade non-Hodgkin's lymphoma (NHL) Ann Arbor stage I-II and limited stage III. PATIENTS AND METHODS: 58 patients, who had been treated between 1980 and 1996, were analyzed. Median follow-up period was 8.75 years. 48 patients (83%) presented with follicular lymphoma (stage I: 23 patients, stage II and III: 15 and ten patients, respectively). Median age was 51 years. Irradiation was applied with a median total dose of 40 Gy. 13 patients (22%) additionally received chemotherapy. End points of the investigation were remission rate, overall- and disease-free survival, and patterns of recurrence, as well as the prognostic impact of age, B-symptoms, chemotherapy, irradiation dose, treatment volume, and Ann Arbor stage. RESULTS: 6 weeks after treatment 91% of the patients had complete, 7% partial response. One patient (2%) was classified as progressive disease. Overall survival rate was 86% and 69% at 5 and 10 years, respectively. Corresponding disease-free survival rates were 73% and 63%. Regarding overall survival, multivariate analysis identified age (p = 0.001) as independent prognostic factor. In the subgroup of patients with follicular lymphoma 92% were found in complete, 6% in partial remission, one patient (2%) with progressive disease. Overall survival rates at 5 und 10 years were 87% and 70%, disease-free survival rates 75% and 64%, respectively. Out-of-field recurrence rate for all 58 patients was 34% and the proportion of relapses at nodal or lymphatic sites outside the treated areas in relation to all registered recurrences was 77%. CONCLUSIONS: Our results maintain external radiotherapy as a curative concept in the treatment of limited stage low-grade lymphoma, especially in younger patients. Patterns of recurrence would favor total nodal irradiation (TNI) as an appropriate approach for these patients.     

Radiotherapy plus a combination of cisplatin and 5-fluorouracil for locally advanced head and neck neoplasms. Study of feasibility and preliminary results

In March 1989 we started a feasibility study of combined radio-chemotherapy in patients with locally-advanced head and neck cancer. The first phase of treatment consisted of conventional radiotherapy (2 Gy/day, 5 days/week for a total dose of 70 Gy to primary tumor and +/- 50 Gy to nodes) and cisplatinum (20 mg/m2, i.v., for 4 days) +5FU (200 mg/m2, i.v., for 4 days) every 4th week, during radiant sessions. The second phase of treatment was started about one month after the end of simultaneous chemotherapy and radiotherapy: patients in complete remission received 1 more cycle of chemotherapy, as consolidation, while patients in partial remission received two more cycles of chemotherapy. Non-responding patients received no more chemotherapy. During the second phase the days of cisplatinum and 5FU were 5. Up to April 1990, 17 patients have been included in the study. They were stage III (64%) and IV (36%). The mean administered dose of radiotherapy was 66 Gy (range: 60-70 Gy) to primary tumor and 60 Gy (range: 40-70 Gy) to nodes. The total number of chemotherapy cycles administered during radiant sessions was 37, the mean number of cycles was 2 (range: 1-3), with 100% dose percentage. The interval between cycles was 3 weeks in 84% of patients. The relationship between number of cycles administered and planned cycle was 37/39 (feasibility: 95%). Acceptability was 100% (no patient refused the treatment). Feasibility of the second phase was 77% and acceptability 90% (1 patient refused the treatment). Toxicity was moderate during the first and the second phases. After the first phase 14/15 evaluable patients (92%) had major response (complete remission: 46%). After the second phase 10/10 evaluable patients had a complete remission. In conclusion, this combined treatment is very easy to administer, and very well accepted. Moreover, it yields a high number of objective responses.     

Carcinoma of the colon: irradiation by delayed split whole-abdominal technique

Locally advanced and recurrent colon cancer was treated by irradiating first the pelvis and two hours later the upper abdomen. Curative treatment consisted of 4,000-5,000 rad (40-50 Gy) in 200-rad (2-Gy) fractions to the pelvis and 3,000 rad (30 Gy) in 150-rad (1.5-Gy) fractions to the upper abdomen. Palliative treatment consisted of 2,100 rad (21 Gy) in 300-rad (3-Gy) fractions to the liver, 3,000 rad (30 Gy) in 150-rad (1.5-Gy) fractions to the upper abdomen, and 4,000-5,000 rad (40-50 Gy) in 200-rad (2-Gy) fractions to the pelvis. Treatment was tolerated well, and acute toxicity was limited. Seven of the 11 patients treated curatively remain free of abdominal disease after 10-35 months; median survival among 9 patients treated palliatively was 9 months.     

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.