Massive endoprosthetic replacement for bone metastases resulting from renal cell carcinoma: Factors influencing patient survival

Background

Surgery remains the main treatment of bone metastases due to renal cell carcinoma (RCC). We reviewed 135 patients treated with resection and endoprosthetic replacement (EPR) and examined clinico-pathological factors predicting survival.

Methods

Surgical and oncological outcomes were examined using a prospectively maintained database between 1976 and 2012. Survival rates were calculated by Kaplan–Meier method. Multivariate analyses were performed to investigate factors predictive of increased survival.

Results

At diagnosis, 81 patients had synchronous RCC and bone metastases and the remaining developed metachronous metastases after primary treatment for RCC. The majority were solitary tumours (75%) and 77% had ≥ one concurrent visceral metastases. The median age at surgery was 61 years old (IQR 53–69). The median follow-up was 20 months (IQR 10–43) and the overall survival was 72% at one-year. This declined to 45% and 28% at three and five-years, respectively. After adjustments for prognostic factors, there was an increased risk of death in patients with multiple skeletal metastases (HR = 2), ≥one visceral metastases (HR = 3) and local recurrence (HR = 3) (all p ≤ 0.01). Ten patients required revision (7%) and the risk of revision was 4% at one-year and remained low at 8% from two years postoperatively.

Conclusion

Patients with solitary bone lesions and no visceral metastases should be considered for bone resection and EPR. As survival beyond one-year can be expected in a majority of patients and the risk of further surgery after EPR is low, patients with multiple skeletal metastases and visceral metastases should also be considered.     

Liver resection for metastatic gastric cancer: experience with 42 patients including eight long-term survivors

BACKGROUND: The indication for liver resection for gastric metastases remains controversial and few previous studies have reported the outcome of surgery in the treatment of liver metastases of gastric cancer. The aim of this study is to clarify the effectiveness of surgical resection for liver metastases arising from gastric cancer. METHODS: A retrospective analysis was performed on the outcome of 42 consecutive patients with synchronous (n = 20) or metachronous (n = 22) gastric liver metastases that were curatively resected. RESULTS: The overall 1, 3 and 5 year survival rates after hepatic resection were 76, 48 and 42%, respectively, and the median survival was 34 months. Univariate analysis revealed that survival significantly differed between cases of solitary and multiple metastases (P = 0.03). Multivariate analysis revealed that solitary liver metastasis and the absence of serosal invasion by primary gastric cancer were favorable independent prognostic factors (P = 0.005 and P = 0.02, respectively). All eight patients who survived for more than 5 years after initial hepatectomy had a solitary metastasis, and six of these had no serosal invasion by the primary gastric cancer. No patient with multiple metastatic diseases survived beyond 3 years. CONCLUSIONS: Patients with a solitary liver metastasis are good candidates for surgical resection, whereas those with multiple gastric liver metastases should be treated by multimodal approaches.     

Results of surgical treatment of pulmonary metastases

From 1970 to 1993, 155 thoracotomies for metastatic lung tumors were performed on 113 patients in the Department of Surgery, Kanazawa University School of Medicine. Overall 30-day mortality amounted to 0.9% (1/113). The cumulative 3- and 5-year survival rates were 39.4% and 29.1%, respectively. The overall median survival was 24 months. The 5-year survival rate for carcinoma was 37.2% and for sarcoma it was 14.5% (P < 0.01). The other significant predictors of better long-term survival with metastatic lung tumors were solitary lesions, disease-free interval (DFI) > 24 months, and tumor size ≤ 20 mm in diameter. There was no significant difference in survival based on the method of pulmonary resection. Repeat thoracotomy for recurrent metastases was performed in 27 patients, whose 5-year survival rate after the first lung resection was 35.5%. For bilateral pulmonary metastases, we recently performed simultaneous bilateral thoracotomy via median sternotomy on 25 patients and transsternal simultaneous bilateral thoracotomy on 8 patients. The latter procedure provides a wide operative field and better survival. We conclude that resection of metastatic lung tumors is safe and effective, and that repeat thoracotomy is warranted in selected patients with recurrent pulmonary metastases. © 1995 Wiley-Liss, Inc.     

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).     

Prognostic Factor Analysis for Multiple Brain Metastases After Gamma Knife Radiosurgery: Results in 97 Patients

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2–4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20Gy (range 17–30Gy). Median tumor volume was 3900cmm (range 100–10000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%).The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n=5) and necrosis (n=1).SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.     

胸腔镜术治疗肺转移瘤的可行性分析

背景与目的:随着内镜外科和影像学技术的进步,胸腔镜术治疗肺转移瘤的应用越来越广泛,本研究拟对胸腔镜术治疗肺转移瘤的可行性进行探讨。方法:对经胸腔镜术治疗的17例肺转移瘤患者的资料进行回顾性分析。结果:本组17例肺转移瘤均为原发肿瘤治疗后随访时发现,均位于肺外周,且排除肺外转移。其中孤立性转移瘤10例,单侧多发转移瘤4例,双侧多发转移瘤3例,全部行胸腔镜下肺楔形切除术。无手术死亡,无术后严重并发症,无切口肿瘤种植。术后局部复发5例,4例为多发肺转移患者,另1例软组织肉瘤孤立转移患者再次行胸腔镜术切除复发性肺转移瘤。1、3、5年生存率分别为77.3%、53.1%和34.8%。结论:对外周肺野、直径≤3cm、特别是孤立性肺转移瘤采用胸腔镜术治疗完全可行、有效,双肺转移瘤亦可一期切除。     

Phase II study of weekly mitoxantrone, 5-fluorouracil,and leucovorin in metastatic breast cancer

Summary A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m², 5-fluorouracil 375 mg/m², and L-leucovorin 100 mg/m² on day 1, weekly. Patient characteristics were: median age 53 years (range 36–65); estrogen receptor (ER) status was known in 26 patients and of these 15 (57.7%) patients were ER-positive and 11 (42.3%) ER-negative. Of the 43 patients, 25 (58.1%) and 18 (41.9%) patients had received prior adjuvant chemotherapy and prior adjuvant endocrine treatment, respectively. MFL was administered to 22 (51.1%) patients as first line chemotherapy for advanced disease, while 21 (48.9%) patients had received 1 to 2 cytotoxic regimens for metastatic disease. The dominant sites of metastases were: soft tissue in 11 (25.5%) patients, bone in 8 (18.6%) patients and viscera in 24 (55.9%). All patients were assessable for toxicity: only 8 patients experienced WHO grade 3 leukopenia. Thrombocytopenia, diarrhea, stomatitis, and nausea/vomiting were negligible. Anemia and alopecia were not observed. Thirty-nine patients were assessable for response: overall response rate was 28.2% (complete response 7.7% and partial response 20.5%). Median duration of response was 12 months (range 6–34). Patients with no prior anthracyclines had a 42.1% response rate compared to 15% in patients who had received anthracyclines. Median overall survival of the 43 patients was 6 months (range 1–34). Weekly MFL is a well-tolerated and a moderately effective regimen for the treatment of metastatic breast cancer.     

Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery

Context: Long-term survival of patients with metastatic colorectal cancer has been achieved only in patients who underwent complete resection of metastases. Such surgery could be performed in a greater proportion of patients if effective chemotherapy could downstage previously unresectable metastases. This approach has been limited by the low tumor response rate achieved with conventional chemotherapy.Objective: We studied the outcome of patients with initially unresectable liver metastases from colorectal cancer treated with a three-drug chemotherapy regimen followed by liver metastases surgery whenever possible.Patients and methods: From March 1988 to June 1994, 151 patients with colorectal liver metastases were considered initially unresectable because of large tumor size (>5 cm), multinodular (>4) or ill-located metastases. All patients received fully ambulatory chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin (chronotherapy in 83% of them). They were periodically reassessed for surgery by a joint medico-surgical team.Results: In 151 patients, the size of liver metastases decreased by >50% in 89 patients (59%) and median overall survival was 24 months (95% confidence interval (95% CI): 19–28 months), with 28% surviving at five years (20%–35%). Surgery with curative intent was attempted in 77 patients (51%), complete resection of liver metastases was achieved in 58 patients (38%). The median survival of the 77 operated patients was 48 months (25–71), with a five-year survival rate of 50% (38–61).Conclusion: This new strategy of combining effective chemotherapy with surgery apparently altered the natural history of unresectable colorectal cancer metastases.     

Mitoxantrone,vincristine, and 5-fluorouracil with leucovorin modulation as induction chemotherapy prior to high-dose intensification in metastatic breast cancer

Summary We treated 39 women with newly diagnosed stage IV breast cancer with a new regimen of mitoxantrone 18 mg/m² on days 1, 29, 57, vincristine 1.4 mg/m² (maximum 2.0 mg) on days 1, 8, 15, 22, 29, 36, 43, 50, and 5-fluorouracil 375 mg/m² on days 15–20, 43–47, 71–75 with leucovorin modulation 500 mg/m² before each 5FU infusion (MVF). This regimen was utilized as an initial cytoreductive or induction program for these patients prior to high-dose intensification with autologous stem cell rescue. Ten patients (25%) obtained a clinical complete response and six patients (15%) obtained a partial response for an overall response rate of 40%. In addition, 10 patients had evaluable disease that was improved or stable (primarily bone and/or bone marrow metastases) after MVF induction. Thus, 26 patients (65%) were eligible for high-dose intensification with autologous stem cell rescue after MVF induction. Toxicity was primarily a mild mucositis and more commonly peripheral neuropathy. MVF therapy is an active treatment program for metastatic breast cancer but the neurotoxicity makes it difficult to recommend for widespread use.     

可切除结直肠癌肺转移的预后因素分析

目的 探讨结直肠癌肺转移根治性切除术后的预后影响因素.方法 回顾性分析行根治性切除术的60例结直肠癌肺转移患者的临床资料.结果 全组患者肺转移瘤切除术后和结直肠癌切除术后的5年生存率分别为43.7%和74.0%.单因素分析结果显示,肺转移瘤数目和无瘤间期与结直肠癌术后患者的总生存率有关(均P＜0.05),肺转移瘤切除前癌胚抗原(CEA)水平、肺转移瘸数目、有无肺门和纵隔淋巴结转移与肺转移瘤切除术后患者的生存率有关(均P＜0.05).多因素分析结果显示,肺转移瘤数目和无瘤间期是结直肠癌术后患者预后的独立影响因素(OR=2.691,95% CI为1.072～6.754;OR=0.979,95% CI为0.963～0.994),肺转移瘤数目、有无肺门和纵隔淋巴结转移是肺转移瘤切除术后患者预后的独立影响因素(OR=3.319,95% CI为1.274～8.648;OR=3.414,95% CI为1.340～8.695).结论 经过严格选择的结直肠癌肺转移患者,尤其是单发肺转移及无肺门和纵隔淋巴结转移的患者,行根治性切除术后可获得长期生存.     

Surgical treatment of hepatic metastases from breast cancer

We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2–132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3±3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.     

Upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer with synchronous liver metastases

BackgroundThe optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.MethodsForty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.ResultsAt the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.ConclusionUpfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.     

Intracranial relapse rates and patterns,and survival trends following post-resection cavity radiosurgery for patients with single intracranial metastases

The objective of this study is to evaluate the patterns of relapse and survival trends in patients with single brain metastases treated with post-operative adjuvant Gamma knife stereotactic radiosurgery (GKS) without whole brain radiotherapy (WBRT). Retrospective analysis of all consecutive patients who underwent GKS to the tumor cavity following resection of solitary brain metastasis was performed at a single institution. Between March 2001 and June 2010, 56 patients underwent GKS to the resection cavity following resection of intracranial metastases; no patient received pre- or post-operative WBRT as an adjuvant (salvage WBRT was permissible). The mean marginal dose was 17.1 Gy (range 14–20 Gy). The mean follow-up period was 24 months (range 3–99 months). Five patients (8.9%) had local recurrence in the immediate vicinity of the resection cavity, qualifying as “local failures”, and 21 (37.5%) recurred at distant intracranial sites. Median intracranial recurrence free survival was 13 months. Median overall survival was 20.5 months. Salvage interventions were required in 26 patients, and included repeat radiosurgery in 17 patients, further surgery in two patients, and salvage WBRT in eight (14.3%; two of whom had also been locally salvaged with repeat radiosurgery) patients. As expected, avoidance of WBRT results in a high rate of intracranial failure (26/56 patients, 46%), even in well-selected patients with only single brain metastases. As anticipated, the majority of failures (21, 37.5%) are “distant intracranial”, and in this well-selected cohort the local failure rate is low (5/56 patients, <9%). All patients failing intracranially (46%) are potential candidates for salvage therapies, but WBRT as salvage was utilized in only 14.3% of patients. The median intracranial relapse-free was 13 months and overall survival was 20.5 months.     

Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases

BackgroundThe benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer.MethodsAmong 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery.ResultsThe overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival.ConclusionsSurgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.     

Experience with continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. A prospective randomized study

Sixty-five patients with hepatic metastases from colorectal primaries were studied in a prospective randomized fashion. The five patients with solitary metastases all had resection of metastases and 50% were randomized to pump therapy. Of the 16 patients with multiple resectable metastases, 7 had pump only and 9 had resection plus pump. Although the difference was not significant, there was a trend of improved survival for the patients with resection plus pump. For the patients with unresectable disease, those patients with positive portal nodes had poor survival matching those patients with extra hepatic metastases. Patients with unresectable disease treated with pump had a 73% therapeutic response rate and a median survival of 22 months. Significant complications included chemical hepatitis and biliary stenosis. The long-term efficacy of continuous hepatic artery infusion versus the hazards of treatment and the financial cost will need further investigation.     

Patterns of metastatic spread following resection of extremity soft-tissue sarcomas and strategies for treatment

This study examines recurrence patterns in 255 patients with soft-tissue sarcoma treated with preoperative chemotherapy and radiation, followed by limb-sparing surgery. Eighty-five patients developed metastatic disease: 13 had isolated local recurrence, 43 had isolated pulmonary metastases, 11 had metastases to lung and elsewhere, and 18 had metastases to multiple sites. Of the patients with isolated pulmonary metastases, 19/43 had resection of the metastases, and 9 are disease free. All 13 patients with local recurrences had resection of the recurrence, and 9 remain disease-free. Patients with multiple sites of recurrence had a 2-year survival of less than 10%. Resection of metastases is beneficial to a small number of patients who develop metastatic disease.     

Breast carcinoma with brain metastases: clinical analysis and immunoprofile on tissue microarrays

BackgroundDevelopment of brain metastasis in patients with breast carcinoma correlates with poor outcome. Identification of tumor characteristics associated with breast cancer brain metastases (BCBM) could help identify patients at risk.Patients and methodsWe studied 209 patients with BCBM. We evaluated a panel of proteins relevant to the biology of breast carcinoma on tissue microarrays of 133 primary tumors and 56 BCBM, including paired samples from 43 patients, and correlated the findings with the clinical outcome.ResultsThe median survival after BCBM diagnosis was 19 months (95% confidence interval, 13–23 months). Patients presenting with solitary metastasis had a significantly longer median survival than those with multiple lesions (25 versus 11 months, P ≤ 0.0001). We found no significant discordance in the expression of tested markers, but identified a possible association between the expression of basal cytokeratin CK5/6 in the primary carcinoma and the development of multiple rather than solitary brain metastases.ConclusionsExpression of antigens commonly associated with breast carcinoma does not differ significantly between the primary tumor and the corresponding brain metastases. Although no specific immunoprofile identifies breast carcinomas that develop brain metastases, we observed a possible association between CK5/6 expression in the primary tumor and multiple versus solitary BCBM.     

Ifosfamide in advanced epidermoid head and neck cancer

Summary A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i. v. doses of 3 g/m² given daily on 3 consecutive days in combination with mesna (600 mg/m²×3 oral daily doses on days 1–3) every 3 weeks. In all, 7 patients showed a partial response and 2 patients achieved a complete response, for an overall objective response rate of 26% (9 of 35 eligible patients; 95% confidence interval, 12.5%–43%). Excluding the 5 early nontoxic deaths observed during the first 3 weeks of therapy, the objective response rate was 30% (9 of 30 patients; 95% confidence interval, 15%–49.5%). Responses were seen in lung metastases (2 patients), lymph nodes (2 patients), skin (3 patients), and cases of local recurrence (5 patients). The median duration of responses was 3 months (range, 2–5 months). The main side effects of ifosfamide were alopecia (83% of patients), emesis (80%), granulocytopenia (23%), and mild mucositis (20%). Two poor-risk patients suffered severe CNS complications that were probably related to treatment. Three patients died due to chemotherapy-related complications (2 patients with CNS toxicity and 1 patient with granulocytopenic sepsis). In conclusion, ifosfamide appears to be an active drug in epidermoid head and neck cancer and merits further evaluation in this disease.     

The relative effectiveness of radiation therapy, corticosteroids, and surgery in the management of melanoma metastatic to the central nervous system

The records of all patients who received radiotherapy for melanoma metastatic to brain (63 patients) and epidural space (9 patients) at the American Oncologic Hospital from January, 1971, through March, 1980, were reviewed. Patients were evaluated according to the type of therapy received (corticosteroids, radiotherapy, surgery) and whether their brain metastases were radiographically solitary (60%) or multiple (40%). Forty-nine patients with brain metastases received corticosteroid therapy for 2 to 7 days or more before radiotherapy. Seventy-three percent of these patients had documented responses to corticosteroids. This was substantially higher than the 42% overall response rate that could be attributed to radiotherapy. Fifty-two percent of the patients with solitary and 30% of those with multiple brain metastases responded to radiotherapy. The use of large doses (≥500 rad) per fraction produced a significantly higher response rate than did the use of low doses (≤400 rad) per fraction (P < .02), but only for those patients with solitary brain metastases. Fraction size had no effect on the duration of response or survival. Patients with irradiated solitary brain metastases had a longer duration of response and survival than did those with irradiated multiple brain metastases, but not significantly so. Patients undergoing surgical excision of a solitary brain metastasis and radiotherapy had significantly longer median durations of response (405 days versus 57 days; P = .0047) and survival (448 days versus 96 days; P = .0013) than did patients with solitary brain metastases who did not receive surgery. Re-irradiation was of benefit in relieving recurrent neurologic symptoms, but responses were short and survival was not prolonged. Patients with cord compression undergoing decompressive laminectomy had relief of neurologic symptoms, whereas those not paralyzed who received radiotherapy alone did not respond. Surgical excision with postoperative irradiation is recommended for the management of solitary brain metastases from melanoma. Surgical decompression is recommended for the management of epidural cord compression.     

Properly selected patients with multiple brain metastases may benefit from aggressive treatment of their intracranial disease

To determine whether properly selected patients with multiple brain metastases benefit from aggressive treatment of their intracranial disease, we reviewed 52 patients having stereotactic radiosurgery (SRS), tumor resection, or both between April 1997 and March 2000. Tumor histology included lung (n = 18, 35%), breast (n = 11, 21%), renal (n = 6, 12%), melanoma (n = 6, 12%), and other (n = 11, 21%). The median patient age was 58 years, the median Karnofsky performance status (KPS) was 90, and the median number of tumors was three. Twenty patients (39%) had progressed after prior radiation therapy. Treatment included multiple craniotomies and tumor resection (n = 5, 10%), radiosurgery (n = 31, 60%), or resection and radiosurgery (n = 16, 30%). Median survival was 15.5 months. The one- and two-year actuarial survivals were 63% and 27%, respectively. Multivariate analysis found radiation therapy oncology group recursive partitioning analysis (RTOG RPA) Class (1 vs. 2/3) correlated with improved survival (Relative risk = 2.60, 95% CI 1.13–5.97, p = 0.03). Class 1 patients (KPS 70, age > 65 years, and controlled primary with no extracranial metastases) survived a median of 19 months whereas Class 3 patients (KPS > 70) survived 8 months. Class 2 patients (all other patients) survived a median of 13 months. Thirty-five patients (67%) had intracranial progression at a median of 8.0 months. Intracranial progression was local (n = 6), distant (n = 23), or local and distant (n = 6); 26 patients with intracranial progression underwent additional brain tumor treatments. Multivariate analysis found patients with radiosensitive tumors (lung, breast, other) had fewer intracranial recurrences compared to patients with radio-resistant tumors (melanoma, renal, sarcoma) (Relative risk = 2.43, 95% CI 1.13–5.10, p = 0.02). The length of survival in our series is quite comparable to historical reports on the management of brain metastasis patients, and supports aggressive intervention for RTOG RPA Class 1 patients and Class 2 patients with controlled primary disease who have a limited number of brain metastases.