Spinal Drop Metastases in Recurrent Glioblastoma Multiforme

Summary  Multifocal dissemination of glioblastomas is very rare but is increasing as patients live longer. Between April 1994 and December 1997 one hundred and fifty one patients with a histologically proven glioblastoma multiforme were operated on in the Neurosurgical Department of the University of Kiel, Germany. Recurrent tumours of these patients were removed in 36 patients. Two patients developed multifocal spread of glioblastoma multiforme including spinal drop metastases. Both patients died 10 and 7 months after the primary operation. On histological examination both tumours showed wide perivascular tumour-cell cuffings in the surrounding brain tissue, so that this perivascular growth might be another explanation for the dissemination in these glioblastomas.     

Survival after Stereotactic Radiosurgery for Recurrent Glioblastoma Multiforme

This retrospective analysis details the experience of a tertiary care center with survival and results for patients with recurrent glioblastoma multiforme (GBM) treated with stereotactic radiosurgery (SRS). Between August 1990 and June 1999, 23 patients were treated for recurrent GBM with SRS using either modified 6-MV linear accelerator (linac) or -knife. Twenty-two patients (96%) had an initial histological diagnosis of GBM, while 1 patient had an initial diagnosis of anaplastic astrocytoma that was biopsied at recurrence and found to have upgraded to GBM. The median Karnofsky performance score at the time of SRS was 80; the median age was 53. The median-treated tumor volume was 9.9 cm³, with a dose of 15 Gy delivered to the 60% isodose line. Median progression-free survival was 4.7 months. Median survival time after SRS was 10.3 months. No prognostic factors were found to be significant. Patients with a KPS of 80 or higher had longer median survival times than those with lower KPS scores, but this was not found to be statistically significant. Our results suggest that for selected patients with recurrent GBM, SRS appears to be an appropriate salvage therapy.     

Stereotactic Radiosurgery for Brain Metastases From Breast Cancer

Background: Stereotactic radiosurgery is an alternative to resection or to radiotherapy alone for patients with brain metastases. Outcomes after radiosurgery for patients with brain metastases specifically from breast cancer have not been defined.Methods: We retrospectively studied survival and tumor control for all patients with brain metastases from breast cancer who underwent gamma knife stereotactic radiosurgery at the University of Pittsburgh. Univariate and multivariate analyses were used to determine which prognostic factors significantly affected survival.Results: Thirty patients underwent radiosurgery between 1990 and 1997. A total of 58 metastases were treated. The median length of survival for all patients was 13 months from radiosurgery and 18 months from diagnosis of brain metastases. The tumor control rate on follow-up imaging was 93%. On multivariate analysis, the only factor that correlated with longer survival was the absence of multiple brain metastases. Age, presence of systemic disease, previous whole brain radiation, location, and total tumor volume did not significantly affect survival. Four patients had tumors with evidence of radiation-induced edema after radiosurgery but did not require resection. Two patients underwent delayed resection for tumor growth after radiosurgery.Conclusions: Stereotactic radiosurgery is an effective treatment for brain metastases from breast cancer and is associated with a low complication rate.     

Spinal Glioblastoma Multiforme: Unusual Cause of Post-Traumatic Tetraparesis

Abstract

Background/Objective: Glioblastoma multiforme (GBM) is the most common glial cell tumor of the adult brain. However, primary GBM of the spinal cord is a rare condition.

Methods: Case report.

Results: A young man presented with acute onset quadriparesis after a whiplash injury. A magnetic resonance scan showed the typical appearance of a high-grade intramedullary tumor with fusiform expansion of the entire cervical cord. Subtotal decompression and biopsy was done by posterior laminectomy, followed by external beam radiotherapy. Signs and symptoms improved after the completion of radiotherapy but did not resolve completely. Death caused by respiratory failure occurred 3 months later. Conclusions: This presentation of GBM of the cervical cord is rare; an intramedullary tumor should be considered when minor cervical trauma results in disproportionate neurologic deficit. To the best of our knowledge, this is the first reported case of spinal GBM with extensive pan-cervical involvement.     

Spinal Glioblastoma Multiforme: Unusual Cause of Post-Traumatic Tetraparesis

Background/Objective:

Glioblastoma multiforme (GBM) is the most common glial cell tumor of the adult brain. However, primary GBM of the spinal cord is a rare condition.

Methods:

Case report.

Results:

A young man presented with acute onset quadriparesis after a whiplash injury. A magnetic resonance scan showed the typical appearance of a high-grade intramedullary tumor with fusiform expansion of the entire cervical cord. Subtotal decompression and biopsy was done by posterior laminectomy, followed by external beam radiotherapy. Signs and symptoms improved after the completion of radiotherapy but did not resolve completely. Death caused by respiratory failure occurred 3 months later.

Conclusions:

This presentation of GBM of the cervical cord is rare; an intramedullary tumor should be considered when minor cervical trauma results in disproportionate neurologic deficit. To the best of our knowledge, this is the first reported case of spinal GBM with extensive pan-cervical involvement.     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

Five-Year Survival Following Hepatic Resection After Neoadjuvant Therapy for Nonresectable Colorectal [Liver] Metastases

Background: Surgical resection is the most effective treatment for colorectal liver metastases but only a minority of patients are candidates for a potentially curative resection. Our experience with neoadjuvant chemotherapy followed by resection and five years survival analysis of the patients treated is presented.Methods: Between February of 1988 and September of 1996, 701 patients with unresectable colorectal liver metastases were treated with neoadjuvant chemotherapy. Four categories of nonresectable disease were defined: large size, ill location, multinodularity, and extrahepatic disease. Liver resection was performed in those patients whose disease became resectable. After resection, the patients were followed up every 3 months. A 5-year survival analysis by the different categories described was performed.Results: Ninety-five patients (13.5%) were found to be resectable on reevaluation and underwent a potentially curative resection. There was no perioperative mortality, and the complication rate was 23%. As of December of 1999, 87 patients have completed 5 years of follow-up. The overall 5-year survival is 35% from the time of resection and 39% from the onset of chemotherapy. Respective 5-year survival rates are 60% for large tumors, 49% for ill-located lesions, 34% for multinodular disease, and 18% for liver metastases with extrahepatic disease. In this latter category, however, a 35% 5-year survival was found when all the patients with extrahepatic disease were analyzed rather than only those for whom extrahepatic disease was the main cause of nonresectability.Conclusions: Neoadjuvant chemotherapy enables liver resection in some patients with initially unresectable colorectal metastases. Long-term survival is similar to that reported for a priori surgical candidates.     

结直肠癌切除同期射频消融联合化疗治疗肝转移

目的：探讨结直肠癌切除同期射频消融联合化疗治疗肝转移的临床疗效。方法：对39例病人先行原发肿瘤的切除，同期行射频消融联合化疗治疗肝转移，以螺旋CT增强扫描为主结合彩超综合评价治疗效果。结果：39例共82个肝转移病灶，完全坏死率85％。随访时间〉6个月者3l例，生存27例；随访时间〉12个月11例，生存8例。结论：结直肠癌切除同期射频消融联合化疗治疗肝转移的疗效较好，值得临床推广。     

Liver Resection for Primarily Unresectable Colorectal Metastases Downsized by Chemotherapy

This study was performed prospectively to assess the effect of systemic chemotherapy (FOLFIRI protocol) in patients with initially unresectable colorectal liver metastases (CRLM) and, after performing liver resection in patients with downsized metastases, to compare the postoperative and long-term results with those of patients with primarily resectable CRLM. Records from a prospective database including all consecutive admissions for CRLM between June 2000 and June 2004 were reviewed. The analysis addressed all patients who underwent hepatectomy for primarily resectable CRLM (Group A), or underwent chemotherapy for primarily unresectable CRLM and among these, particularly the patients who were finally resected after downsizing of CRLM (Group B). There were 60 primarily resected patients (Group A). Forty-two other patients underwent chemotherapy; after an average of nine courses, 18 of them (42.8%) with significantly downsized lesions were explored and 15 (35.7%, Group B) were resected, whereas three had peritoneal metastases. Group B differed from Group A for a significantly higher rate of synchronous CRLM upon diagnosis of colorectal cancer, a larger size of CRLM upon evaluation in our center, and a lower rate of major hepatectomies (20.0% vs. 51.6 %) at surgery. No patient in Group B had positive margins of resection. Operative mortality was nil and morbidity was 20.0% in both groups. In Group B vs. Group A median survival after hepatectomy was 46 vs. 47 months (n.s), 3-year survival rate was 73% vs. 71% (n.s.), disease-free survival rate was 31% vs. 58% (p = 0.04) and, at a median follow-up of 34 months, tumor recurrence rate was 53.3% vs. 28.3% (n.s.). Four out of the eight Group B patients with recurrence underwent a re-resection, and were alive at 9 to 67 months after the first resection. These results show that in about one-third of the patients with primarily unresectable CRLM, downsizing of the lesions by chemotherapy (FOLFIRI protocol) permitted a subsequent curative resection. In these patients, operative risk and survival did not differ from the figures observed in primarily resectable patients and, in spite of a lower disease-free survival with more frequent recurrence, re-resection still represented a valid option to continue treatment. Presented at the 2005 Surgical Spring Week AHPBA Meeting (April 14–17, 2005, Fort Lauderdale, Florida).     

Glioblastoma Multiforme after Radiotherapy for Metastatic Brain Tumor of Testicular Cancer

A patient with left testicular cancer and metastases to retroperitoneal lymph nodes, lung, and brain was treated by chemotherapy, radiotherapy and surgery, and obtained the state of no evidence of disease, but 10 years after radiotherapy, a glioblastoma multiforme tumor appeared in the brain. This is the first report of a glioma appearing after radiotherapy in a testicular cancer patient.     

The Status of Stereotactic Radiosurgery for Cerebral Metastases in 1998

The last decade has witnessed an exponential proliferation of radiosurgery facilities in the United States and around the globe, and consequently, several tens of thousands of patients have undergone this procedure for a variety of intracranial and skull-base abnormalities. Since brain metastases represent the most common intracranial neoplasm, these have become a common target for radiosurgery. We present a review paper summarizing the major issues surrounding the management of brain metastases as well as an English-language literature review of 20 independent reports, using either -knife or linear accelerator-based radiosurgery, with >1250 patients and >2100 lesions available for analysis. Variable reporting in the studies precludes a definitive analysis and comparison of all factors in a rigorous statistical fashion, but the composite data reveal an average local control rate of 83% and a median survival of 9.6 months, which are comparable to those in recent surgical reports. Prognostic factors for survival are beginning to be unraveled, and the most important ones appear to be the presence of fewer than three lesions, controlled extracranial disease, and Karnofsky performance score. The exact impact of dose has not been clarified, but a dose–response relationship, especially for 18 Gy, is emerging. The role of whole-brain radiotherapy remains unresolved; it may enhance local control but does not convincingly improve survival and, in some series, is associated with an increased risk of late complications, which appear to be less than 5% on average. The concerns regarding chronic steroid dependance and increased intracranial edema do not appear to be a common problem. With such a large base of uncontrolled evidence, this is an opportune time for conducting and completing randomized trials to validate these observations.     

Multiagent Chemotherapy for Isolated Colorectal Liver Metastases: A Single-centered Retrospective Study

Background  Few studies identifying variables associated with prognosis after resection of colorectal liver metastases (CLM) account for treatment with multiagent chemotherapy (fluoropyrmidines with irinotecan, oxaliplatin, bevacizumab, and/or cetuximab). The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM. Methods  Demographics, clinicopathologic tumor characteristics, treatments, and long-term outcomes were reviewed. Results  From 1996 to 2006, 230 patients underwent resection of CLM. Treatment strategies before and after resection included fluoropyrimidine monotherapy (n = 34 and n = 39), multiagent chemotherapy (n = 81 and n = 73), and observation (n = 115 and n = 118). Prehepatectomy treatment strategy was not associated with overall survival. Actuarial 4-year survival was 63%, 39%, and 40% for patients treated with multiagent chemotherapy, fluoropyrimidine monotherapy, and observation after hepatectomy, p = 0.06. Posthepatectomy multiagent chemotherapy (p = 0.04, HR 0.52 [0.27–1.03]), duration of posthepatectomy chemotherapy treatment of 2 months or longer (p = 0.05, HR 0.49 [0.25–0.99]), carcino-embryonic antigen level >10 ng/mL (p = 0.03, HR 2.09, 95% CI [1.32–3.32]), and node positive primary tumor (p = 0.002, HR 1.79 [1.06–3.02]) were associated with overall survival in multivariate analysis. Conclusions  The association of posthepatectomy multiagent chemotherapy with overall survival in this retrospective study indicates the need for prospective randomized trials comparing multiagent chemotherapy and fluoropyrimidine monotherapy for CLM.     

Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

Long-Term Survival After Repeat Resections of Metastases in Liver, Lung, and Stomach from Sigmoid Colon Cancer: Report of a Case

A 74-year-old female patient underwent a simultaneous colectomy and hepatectomy for sigmoid colon cancer and its hepatic metastases. Six months later she underwent a hepatectomy for recurrent hepatic metastases; then 10 months later, a pulmonary resection for pulmonary metastasis; and 24 months later, a partial gastrectomy for gastric metastasis. As of December 2005, at 7 years 6 months after the first surgery and at 4 years after the last surgery, the patient is still alive with a good quality of life and no sign of recurrence.     

Hepatic Arterial Infusion and Systemic Chemotherapy for Breast Cancer Liver Metastases

Hepatic failure from breast cancer liver metastases (BCLM) is a major cause of morbidity and mortality. We reviewed the treatment histories and outcomes of nine patients with heavily treated BCLM, who received hepatic arterial infusion (HAI) of floxuridine (FUDR)/dexamethasone (Dex) and systemic chemotherapy at our institution. Patients received a median of five (range 1–15) HAI treatments. There were seven (78%) objective responses. Four patients had grade 3 elevations in liver enzymes attributable to HAI. There were no treatment‐related deaths. Median hepatic and extrahepatic time to progression on HAI were both 6 months. Median survival after starting HAI was 17 months (range 1–115). Median overall survival from the original breast cancer diagnosis was 110 months (range 52–248). One patient is alive with stable disease on systemic therapy alone. HAI and systemic chemotherapy is feasible and can benefit selected patients with BCLM, who have progressed on prior therapies. Patients require close monitoring for treatment‐limiting toxicities.     

Preoperative Apparent Diffusion Coefficient of Peritumoral Lesion Associate with Recurrence in Patients with Glioblastoma

Additional resection beyond contrast enhanced lesion on MRI is recently considered to prolong survival in glioblastoma. Prediction of future recurrent site in the peritumoral lesion on preoperative MRI could be useful for surgical planning. The objective of this study was to determine if the preoperative ADC value was associated with the site of future recurrence in patients with glioblastoma. We retrospectively analyzed 21 patients with primary GBM. The ADC value on MRI were analyzed before and after operation and at recurrence. The region of interests (ROIs) were set to cover almost the FLAIR high-signal lesion surrounding contrast enhanced lesion. We determined whether the value of ADC on MRI was correlated with the spot of future recurrence. Among 1844 ROIs determined in the FLAIR high-signal lesion on preoperative MRI, new enhanced lesions occurred in 186 sites. The other 1258 sites showed no change or decrease in size on follow up MRI, and the other 400 sites were removed in first operation. The pre-operative ADC values of sites corresponding to future recurrence were significantly lower than that of non-recurrent sites (p <0.001). We suggest that a low ADC values in FLAIR high-signal lesion is corresponding to recurrence, and useful for predicting recurrence of the lesion in cases of GBM. These results will be helpful for planning of surgery or radiation therapy and facilitate future prospective studies on GBM.     

Perioperative Morbidity Affects Long-Term Survival in Patients Following Liver Resection for Colorectal Metastases

Background Hepatic resection is the treatment of choice in patients with colorectal liver metastases. Perioperative morbidity is associated with decreased long-term survival in several cancers. The aim of this study was to assess the impact of perioperative morbidity and other prognostic factors on the outcome of patients undergoing liver resection for colorectal metastases. Methods One hundred ninety seven patients undergoing liver resection with curative intent were investigated. The influence of prognostic factors, such as complications, tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow obstruction, and era and type of resection, was assessed using univariate and multivariate analysis. Complications were graded using an objective surgical complication classification. Results The 5-year survival rate was 38%, with a median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%. The perioperative morbidity and mortality rates were 30 and 2.5%, respectively. The median survival of patients with perioperative complications was 3.2 years, compared to 4.4 years in those patients without complications (p < 0.01). For patients with positive resection margins, the median survival was 2.1 years, compared 4.4 years in patients with a margin (p = 0.019). Conclusion Perioperative morbidity and a positive resection margin had a negative impact on long-term survival in patients following liver resection for colorectal metastases. This paper has been presented at the annual meeting of the Royal Australian College of Surgeons 2006 and was accepted for oral presentation at the IHPBA 2006 meeting in Edinburgh.     

Recurrence and Survival Outcomes after Hepatic Resection with or without Cryotherapy for Liver Metastases from Colorectal Carcinoma

Background Some reports support resection combined with cryotherapy for patients with multiple bilobar colorectal liver metastases (CRLM) that would otherwise be ineligible for curative treatments. This series demonstrates long-term results of 415 patients with CRLM who underwent resection with or without cryotherapy. Methods Between April 1990 and January 2006, 291 patients were treated with resection only and 124 patients with combined resection and cryotherapy. Recurrence and survival outcomes were compared. Kaplan-Meier and Cox-regression analyses were used to identify significant prognostic indicators for survival. Results Median length of follow-up was 25 months (range 1–124 months). The 30-day perioperative mortality rate was 3.1%. Overall median survival was 32 months (range 1–124 months), with 1-, 3- and 5-year survival values of 85%, 45% and 29%, respectively. The overall recurrence rates were 66% and 78% for resection and resection/cryotherapy groups, respectively. For the resection group, the median survival was 34 months, with 1-, 3- and 5- year survival values of 88%, 47% and 32%, respectively. The median survival for the resection/cryotherapy group was 29 months, with 1-, 3- and 5-year survival values of 84%, 43% and 24%, respectively (P = 0.206). Five factors were independently associated with an improved survival: absence of extrahepatic disease at diagnosis, well- or moderately-differentiated colorectal cancer, largest lesion size being 4 cm or less, a postoperative CEA of 5 ng/ml or less and absence of liver recurrence. Conclusions Long-term survival results of resection combined with cryotherapy for multiple bilobar CRLM are comparable to that of resection alone in selected patients.     

LINAC Radiosurgery for Patients with a Limited Number of Brain Metastases

Patients (pts) with brain metastases have a high risk of cancer-related death due to extra- or intracranial tumor manifestations. The present retrospective analysis demonstrates the ability of linear accelerator (LINAC)-based radiosurgery to control intracranial disease and prolong survival in pts with one to three metastases. From 1991 to 1996, 106 pts (42 females, 64 males; median age, 57 years) with cerebral metastases were treated by stereotactic radiosurgery with a LINAC (8 MeV) equipped with tertiary collimators. In 70 pts, a single metastasis was present; 36 pts had two or three metastases. Fifty-nine pts were treated for their first occurrence of brain metastases; 47 pts had been treated prior to radiosurgery by resection and/or whole-brain irradiation. Histology of the primary tumor was non–small cell lung cancer (36 pts), melanoma (20 pts), breast cancer (15 pts), hypernephroma (15 pts), and other (20 pts). All together, 157 metastases (0.04–69.0 ml; median, 2.7 ml) were irradiated with marginal doses of 12–25 Gy (median, 20 Gy) referred to the 65–80% isodose. Seventy-two percent of the lesions were treated with a single isocenter. Adjuvant whole-brain irradiation was applied in six pts. One hundred thirty-five of 157 metastases were evaluated for response: complete response (CR), 24%; partial response, 31%; no change, 30%; and progression of disease, 15%. CR rates were highest (48%) in small metastases (<1-cm diameter), independent of histological type and dose. The overall median survival was 8 months. Multivariate Cox regression analysis revealed a significant impact on survival for Karnofsky performance score, presence of extracranial tumor, and volume of largest metastasis. Freedom from neurological death was determined only by the volume of the largest metastasis. Patients with multiple metastases and/or extracranial disease had a higher risk of developing new outfield brain metastases. Due to salvage therapy (second or third course of stereotactic radiosurgery, whole-brain irradiation, surgery), the overall survival in pts with two or three metastases did not significantly differ from that in pts with single metastases. LINAC-based stereotactic radiosurgery in pts with up to three cerebral metastases results in survival rates approaching those of pts with resected single brain metastases. As pts with both single and multiple metastases can effectively be salvaged after receiving radiosurgery, extracranial tumor activity becomes a major determinator of survival.