Pretreatment Karnofsky Research Articles

Clinical Results and Hematologic Predictors of Linear Accelerator–Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study

This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (linac)-based, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Between January 2011 and November 2021, 101 consecutive elderly patients with BM were treated by linac-based SRS or fSRT using linac with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. The tumors originated from the lungs (n = 90, 89.1%), colon (n = 2, 2.0%), and others (n = 9, 8.8%) in these EPs. The median pretreatment Karnofsky Performance Scale (KPS) score was 80 (range: 40–100). The median follow-up time was 10 (range: 0–76) months, as was the median survival time. The 6-month and 1 and 2-year survival rates in the EP group were 58.3%, 43.2%, 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years were 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs were 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio (NLR) >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (p<0.001). In the EPs, the prognostic factors associated with prolonged survival time in the Cox proportional hazards model were being female and a good pretreatment KPS score. The findings of our study highlight the efficacy of linac-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. NLR can be an important factor in treatment decisions for EPs with BMs.

Early Reduction in C-Reactive Protein Following Treatment for Spinal Epidural Abscess: A Potential Treatment Guide.

Retrospective Cohort Study. To assess the predictive value of early C-reactive protein (CRP) trends following diagnosis of spinal epidural abscess (SEA). Non-operative management with intravenous antibiotics has not demonstrated equivalent outcomes with regard to mortality and morbidity. Knowledge of specific patient and disease factors associated with worse outcomes may predict treatment failure. All patients treated for spontaneous SEA in a tertiary centre in New Zealand over a 10-year period were followed for at least 2years. CRP at diagnosis and day 4-5 following treatment initiation was analyzed to determine predictors of CRP reduction of at least 50%. Proportional Cox hazards regression investigated mortality over 2years. 94 patients met inclusion criteria and with CRP values available for analysis. Median age was 62years (+/- 17.7) and 59 (63%) were treated operatively. Kaplan-Meier analysis estimate of 2-year survival was .81 (95% CI .72-.88). CRP reduction by 50% was seen in 34 patients. Patients who did not experience a 50% reduction were more likely to have thoracic infection (27 vs 8, P = .02) or multifocal sepsis (41 vs 13, P = .002). Failure to achieve a 50% reduction by day 4-5 was associated with worse post-treatment Karnofsky scores (70 vs 90, P = .03) and longer hospital stay (25days vs 17.5days, P = .04). Cox regression model showed mortality predicted by Charlson Comorbidity Index, thoracic location of infection, pre-treatment Karnofsky score, and failure to achieve a 50% CRP reduction by day 4-5. Patients who fail to reduce CRP values by 50% at day 4-5 following treatment initiation are more likely to experience prolonged hospital stay, have poorer functional outcome and have greater mortality risk at 2years. This group has severe illness regardless of treatment type. Failure to achieve a biochemical response to treatment should prompt reassessment.

BT-4 PROGNOSIS OF HISTOLOGICALLY DIAGNOSED GRADE 2-3 IDH-WILD TYPE DIFFUSE GLIOMAS TREATED WITH RADIATION AND TEMOZOLOMIDE

Abstract Although adult diffuse gliomas, IDH-wildtype, histologically diagnosed as grade 2-3 have been regarded as clinically equivalents with glioblastomas, the prognosis of this population has scarcely been discussed with further consideration of treatment backgrounds. This retrospective study aimed to investigate the prognosis of adult patients with IDH-wildtype diffuse gliomas histologically diagnosed as WHO grade 2-3 using a cohort with homogenous treatment background. A total of 214 IDH-wildtype cases were extracted from the collected data of the previous study investigating the prognostic significance of molecular markers (Arita, Acta Neuropathol Commun 2016). The inclusion criteria were as follows: supratentorial tumor, pretreatment Karnofsky Performance status of 70 or higher, wildtype-H3.3 status, chemoradiation therapy with temozolomide after the initial surgery. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier methods. The histological diagnosis in this study was made based on the WHO 2016 classification, and the histological criteria is compatible with the current classification (CNS WHO5).The mean age was 62.8, 59.8 and 60.2 years in grade 2 (n=8), 3 (n=45) and 4 (n=161) case, respectively. The higher ratio of biopsy cases was associated lower grades (50% in grade 2, 22% in grade 3 and 9% in grade 4 cases). Grade 2-3 cases showed short survival (OS 24.7 months and PFS 9.7months) despite the intensive treatment of chemoradiation at the time of diagnosis. In details, OS was 41.5, 23.1 and 17.8 months in grade 2, 3 and 4 cases, respectively. PFS was 12.6, 9.7 and 8.2 months in grade 2, 3 and 4 cases, respectively. Our results revealed that IDH-wildtype grade 2-3 cases showed dismal prognosis even after the chemoradiation at the time of diagnosis. Further development of treatments is needed in this population as well as glioblastomas, IDH-wildtype.

Long-Term Survival after Linac-Based Stereotactic Radiosurgery and Radiotherapy with a Micro-Multileaf Collimator for Brain Metastasis.

Background: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. Results: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. Patients aged ≥ 71years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76years and < 76years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

MET-01 Linac-based fractionated stereotactic radiotherapy with micro-multileaf collimeter for large brain metastasis unsuitable for surgical resection

To assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018, we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor >30mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n=17, 81%), ovary (n=2, 9.5%), rectum (n =1, 4.8%), and esophagus (n=1, 4.8%). The median pretreatment Karnofsky Performance Status was 50 (range: 50~80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1~86 months). The range of tumor volume was 8.7~26.5 cm3 (median: 17.1 cm3). All patients were basically treated with fSRT ranged from 35 Gy with 7 Gy daily fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

Management of Non–Small-Cell Lung Cancer Patients Initially Diagnosed With 1 to 3 Synchronous Brain-Only Metastases: A Retrospective Study

BackgroundThe treatment options for newly diagnosed non–small-cell lung cancer (NSCLC) patients with 1 to 3 synchronous brain metastases (BM) remain controversial. The current study aimed to comprehensively analyze the characteristics, local treatment paradigms, and survival outcomes in these populations. Patients and MethodsA total of 252 NSCLC patients initially diagnosed with 1 to 3 synchronous brain-only metastases were enrolled onto this study. Local therapy (LT) to primary lung tumors (PLT) and BM included surgery, radiotherapy, or both. Median overall survival (mOS) was measured among patients who received LT to both PLT and BM (all-LT group), patients who were treated with LT to either PLT or BM (part-LT group), and patients who did not receive any LT (non-LT group). ResultsThe mOS for all-LT (n = 70), part-LT (n = 113), and non-LT (n = 69) groups was 33.2, 18.5, and 16.8 months, respectively (P = .002). The OS rates at 5 years for the all-LT, part-LT, and non-LT groups were 25.5%, 16.2%, and 0, respectively. Multivariable analysis revealed that all-LT versus non-LT, pretreatment Karnofsky performance status > 70, histology of adenocarcinoma, thoracic stage I-II, EGFR mutation, ALK positive, and second-line systemic therapies were independent prognostic factors for improved mOS. ConclusionsThe current study showed that LT for both PLT and BM is associated with superior OS in appropriately selected NSCLC patients initially diagnosed with 1 to 3 synchronous BM. Prospective trials are urgently needed to confirm this finding.

Linac-based fractionated stereotactic radiotherapy with a micro-multileaf collimator for large brain metastasis unsuitable for surgical resection.

The aim of this study was to assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018 we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor with ≥30 mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n = 17, 81%), ovary (n = 2, 9.5%), rectum (n = 1, 4.8%) and esophagus (n = 1, 4.8%). The median pretreatment Karnofsky performance status was 50 (range: 50–80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1–86 months). The range of tumor volume was 8.7–26.5 cm3 (median: 17.1 cm3). All patients were basically treated with 35Gy in 5 fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

Linac-Based Fractionated Stereotactic Radiotherapy with a Micro-Multileaf Collimator for Brainstem Metastasis

To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n= 18, 75.0%), colon (n= 3, 12.5%), and breast (n= 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.

Prognostic and predictive factors for clinical and radiographic responses in patients with painful bone metastasis treated with magnetic resonance-guided focused ultrasound surgery

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis.Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses.Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF <70% were 91.7% and 52.6%, respectively (p = 0.0235).Conclusion: The pretreatment KPS was an independent prognostic factor for clinical responses, and lesion CVF was an independent prognostic factor for radiographic responses.

Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Glioblastoma of the Corpus Callosum.

Glioblastoma of the corpus callosum is particularly difficult to treat, as the morbidity of surgical resection generally outweighs the potential survival benefit. Laser interstitial thermal therapy (LITT) is a safe and effective treatment option for difficult to access malignant gliomas of the thalamus and insula. To assess the safety and efficacy of LITT for the treatment of glioblastoma of the corpus callosum. We performed a multicenter retrospective analysis of prospectively collected data. The primary endpoint was the safety and efficacy of LITT as a treatment for glioblastoma of the corpus callosum. Secondary endpoints included tumor coverage at thermal damage thresholds, median survival, and change in Karnofsky Performance Scale score 1 mo after treatment. The study included patients with de novo or recurrent glioblastoma of the corpus callosum (n = 15). Mean patient age was 54.7 yr. Mean pretreatment Karnofsky Performance Scale score was 80.7 and there was no significant difference between subgroups. Mean tumor volume was 18.7 cm3. Hemiparesis occurred in 26.6% of patients. Complications were more frequent in patients with tumors >15 cm3 (RR 6.1, P = .009) and were associated with a 32% decrease in survival postLITT. Median progression-free survival, survival postLITT, and overall survival were 3.4, 7.2, and 18.2 mo, respectively. LITT is a safe and effective treatment for glioblastoma of the corpus callosum and provides survival benefit comparable to subtotal surgical resection with adjuvant chemoradiation. LITT-associated complications are related to tumor volume and can be nearly eliminated by limiting the procedure to tumors of 15 cm3 or less.

LL-03 * STEREOTACTIC RADIOSURGERY FOR SALVAGE TREATMENT OF RECURRENT CNS LYMPHOMA

BACKGROUND: Primary and secondary central nervous system lymphoma (PCNSL, SCNSL) are typically treated with chemotherapy and external beam radiation therapy (EBRT). There is no standard salvage therapy for either. The role of stereotactic radiosurgery (SRS) as salvage therapy in PCNSL and SCNSL is poorly defined. METHODS: A retrospective analysis was performed of all patients having SRS, typically using the Gamma Knife (GK), for recurrent intracranial PCNSL and SCNSL at Mayo Clinic Rochester between 2004 and 2011. RESULTS: Fourteen patients underwent SRS. All had their SRS via the GK. The median patient age was 71 years. Seven patients (50%) had PCNSL and seven patients had SCNSL. All had received prior chemotherapy and 10 patients (71%) had undergone prior EBRT with a median dose of 40 Gy in 25 fractions. The median tumor volume was 6.7 cm3 (range, 0.5-37.7); the median margin dose was 15.5 Gy (range, 10-18). Eleven patients (79%) had tumor regression (n = 11) shown on MRI after SRS. The median overall survival after SRS was 288 days, 472 days for PCNSL and 288 days for SCNSL. Significant factors contributing to survival greater 9 months following SRS, were increased marginal dose (Odds ratio = 7.8, p = 0.006, 95% CI (1.74-188.79), increase in maximal dose (Odds ratio = 1.54, p = 0.008, 95% CI (1.09-2.77), and increase in pre-treatment Karnofsky score (Odds ratio = 4.69, p = 0.001, 95% CI (1.45-75.5). No patient had a major radiation-related complication. CONCLUSION: SRS for patients with recurrent CNS lymphoma is well-tolerated and has a high rate of radiographic response. Survival after SRS varied based on multiple factors including marginal and maximal radiation dose and pretreatment Karnofsky score. Control of microscopic disease using established therapies remains vitally important and is not addressed with SRS. SRS represents a viable therapy for local control of recurrent CNS lymphoma for properly selected patients.

Contraindications to cisplatin based chemoradiotherapy in the treatment of cervical cancer in Sub-Saharan Africa

Background and Purpose We conducted a prospective study to assess the eligibility of patients presenting with cervical cancer in the developing world for chemoradiotherapy. Material and Methods Patients with biopsy proven cervical cancer were eligible. Workup included history, examination, pre-treatment Karnofsky performance score, evaluation under anaesthesia to establish FIGO stage, complete blood count, renal and liver functions tests, HIV test and ultrasound of the abdomen and pelvis. Exclusion criteria: stage IA, stage IV, HIV status positive, Karnofsky performance score <60, age >70 years, hydronephrosis, haemoglobin <8 g/dL, white cell count <2,000/μL, platelets <100,000/μL, creatinine >97 μmol/L. Results 314 patients were included. After workup, 47 patients (15.1%) were eligible for combined modality treatment and 190 (60.5%) were not eligible. Eligibility could not be established in 77 cases (24.4%). 37 (11.6%) of the group were HIV positive, HIV status was not established in 38.4% of cases. The most frequently encountered exclusion criteria were hydronephrosis and anaemia. Application of a haemoglobin cut off point of 8 g/dL for cisplatin based chemotherapy resulted in the exclusion of 55 (17.4%) patients. A limit of 10 g/dL excluded an additional 11 patients. Hydronephrosis was diagnosed on ultrasound in 99 (31.4%) patients. 56% had unilateral hydronephrosis, 44% had bilateral hydronephrosis. Conclusions A small proportion of our patients with cervical cancer would benefit from chemoradiotherapy with concomitant cisplatin, illustrating the difficulties of applying “standard” treatment to the developing world. The introduction of national screening programmes and the provision of accessible radiotherapy facilities should be the major priorities in the developing world setting.

Proposed Treatment Strategy for Cavernous Sinus Meningiomas: A Prospective Study

To establish a safe and effective treatment strategy for cavernous sinus (CS) meningiomas, we prospectively analyzed the outcome of a treatment protocol combining surgery and radiosurgery during the past 7 years. Tumors confined to the CS and distant from the optic apparatus and the brainstem were treated with radiosurgery alone. Tumors attached to or compressing the optic apparatus and brainstem and that were larger than 3 cm in mean diameter, extended into the multiple cranial fossae, and were suspected of being malignant were treated with combined nonradical microsurgery and radiosurgery. In accordance with this treatment protocol, 40 patients aged 26 to 72 years (median, 51 yr) with primary (n = 27) or recurrent (n = 13) CS meningiomas (volume range, 0.9-39.3 cm(3); median volume, 5.4 cm(3)) were treated with combined surgery and radiosurgery (n = 23) or radiosurgery alone (n = 17). During radiosurgery, 12 to 18 Gy (median, 16 Gy) was delivered to the tumor margin. The follow-up period ranged from 14 to 79 months (median, 47 mo). The actuarial tumor control rate was 94.1% at 5 years. The improvement of cranial nerve function was significantly frequent in patients with primary CS meningiomas (P < 0.05). Permanent cranial nerve dysfunction was significantly frequent in patients with tumors compressing the brainstem or smaller than 10 cm(3) (P < 0.05). All 36 patients with a pretreatment Karnofsky Performance Scale score of 90 or more maintained the same range after treatment. Proper combination of microsurgery and radiosurgery for CS meningiomas provides excellent growth control with favorable functional state. Outcomes were better when this protocol was adopted at the initial diagnosis for patients with smaller tumors that did not compress the brainstem.

Survival trends in elderly patients with glioblastoma multiforme: Resective surgery, radiation, and chemotherapy

Background It is appropriate to investigate and to determine survival trends following glioblastoma multiforme treatment using resective surgery, radiation therapy, and/or chemotherapy in patients aged 59 years and higher. Methods We retrospectively reviewed 30 elderly patients (≥59 years old) who were treated for histopathologically confirmed glioblastoma multiforme at our tertiary care institution from 1990 through 2002. All patients were treated with steroids. In addition, 22 patients underwent resective surgery (RS), 17 patients underwent radiation therapy (RT), and 10 patients underwent chemotherapy (C). Many patients underwent these treatments in various combinations: 6 underwent biopsy only, 7 RS only, 6 RS+RT only, and 9 RS+RT+C. For each case, pre-treatment Karnofsky performance scores (KPS), tumor location, presenting symptoms and signs, associated surgical morbidity, and pre-existing medical conditions were also recorded. Patients were categorized into one of four treatment subgroups: Biopsy only, RS only, RS+RT, and RT+RS+C. For each of these subgroups, pretreatment KPS and post-treatment survival were compared. Results Post-treatment survival following biopsy only was 3.2 ± 0.8 months (mean ± SE); RS 2.2 ± 0.5; RS+RT 5.5 ± 1.2; RS+RT+C 13.6 ± 2.1. A longer survival trend was noted for the RS+RT versus RS group (two-tailed unpaired t test, p = 0.02;), as well as the RS+RT+C group, which showed consistently higher survival in comparison to most of the other groups ( p = 0.0021, 0.00039, 0.013 vs. the biopsy only, RS only, and RS+RT groups, respectively). No significant difference was found in KPS, comparing all individual groups versus each other ( p ≥ 0.06). Remarkably, 6 patients survived over 14 months (range, 14.1–22.7 months), all of which received RS+RT+C. Conclusions This study suggests a significant improvement in elderly patients treated with the combination of resective surgery, radiation therapy, and chemotherapy, rather than either treatment alone or other combination. This significant improvement does not appear to be biased by pretreatment KPS, as mean KPS values did not significantly differ between any of these groups. However, a greater number of patients in each group must be considered to achieve the power to make more definitive treatment guidelines.

Quality-adjusted survival after tumor resection and/or radiation therapy for elderly patients with glioblastoma multiforme.

Prognostic factors are poorly defined for the elderly subpopulation with glioblastoma multiforme and have been exclusively related to conventional survival analysis. In this study an additional quality adjusted survival analysis (QAS) was performed. The prognostic evaluation of both survival- and QAS data after standard treatment were checked for concordant/discordant findings. Their usefulness for estimation of treatment effects and treatment strategies was then evaluated. 123 patients >or= 65 years of age with a supratentorial, de novo glioblastoma were included in the current retrospective report. Microsurgery plus radiation therapy (planned tumor dose: 60 Gy) was performed in 58 patients, and radiation therapy alone after stereotactic biopsy (planned tumor dose: 60 Gy) in 65 patients. The functional status of each patient was scored when joining the study and at every follow-up using 15 selected neurological signs and symptoms (NSSs). Gradation of severity of each NSS was performed with subjective weights. Survival time of each patient was adjusted according to any changes in these NSSs to become the Quality Time (Q-TIME). Time intervals spent with side effects of the treatment (TOX) were subtracted from Q-TIME to become the patient's QAS (QAS = Q-TIME-TOX). Prognostic factors for both survival and QAS were obtained from the Cox model. Overall survival and QAS were 24 weeks and 10.5 weeks, respectively. Perioperative morbidity and mortality were 5.2 % and 1.7 % in the surgery group and 1.5 % and 1.5 % in the biopsy group, respectively (p > 0.05). Tumor resection gained favorable prognostic importance for patients with midline shift in terms of both survival and QAS (p < 0.0001). Otherwise, radiation therapy alone was as effective as surgery plus radiation therapy (concordant finding). A pretreatment Karnofsky Score (KPS) < 70 was an unfavorable predictor for QAS (p < 0.002) but not for survival (discordant finding). Median QAS for patients with a pretreatment KPS < 70 was only 10 weeks. Age did not reach prognostic relevance. The dramatic decrease of QAS as compared with survival indicates extremely limited posttreatment improvement and/or rapid deterioration of the neurological score after standard treatment for the older subpopulation with glioblastoma multiforme. Supportive treatment should be considered for patients with a pretreatment KPS < 70.

Gamma Knife Stereotactic Radiosurgery for Patients with Glioblastoma Multiforme

OBJECTIVE Stereotactic radiosurgery (SRS) has become an effective therapeutic modality for the treatment of patients with glioblastoma multiforme (GBM). This retrospective review evaluates the impact of SRS delivered on a gamma knife (GK) unit as an adjuvant therapy in the management of patients with GBM. METHODS Between August 1993 and December 1998, 82 patients with pathologically confirmed GBM received external beam radiotherapy (EBRT) at the University of Maryland Medical Center. Of these 82 patients, 64 with a minimum follow-up duration of at least 1 month are the focus of this analysis. Of the 64 assessable patients, 33 patients were treated with EBRT alone (Group 1), and 31 patients received both EBRT plus a GK-SRS boost (Group 2). GK-SRS was administered to most patients within 6 weeks of the completion of EBRT. The median EBRT dose was 59.7 Gy (range, 28–70.2 Gy), and the median GK-SRS dose to the prescription volume was 17.1 Gy (range, 10–28 Gy). The median age of the study population was 50.4 years, and the median pretreatment Karnofsky performance status was 80. Patient-, tumor-, and treatment-related variables were analyzed by Cox regression analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS Median overall survival for the entire cohort was 16 months, and the actuarial survival rate at 1, 2, and 3 years were 67, 40, and 26%, respectively. When comparing age, Karnofsky performance status, extent of resection, and tumor volume, no statistical differences where discovered between Group 1 versus Group 2. When comparing the overall survival of Group 1 versus Group 2, the median survival was 13 months versus 25 months, respectively (P = 0.034). Age, Karnofsky performance status, and the addition of GK-SRS were all found to be significant predictors of overall survival via Cox regression analysis. No acute Grade 3 or Grade 4 toxicity was encountered. CONCLUSION The addition of a GK-SRS boost in conjunction with surgery and EBRT significantly improved the overall survival time in this retrospective series of patients with GBM. A prospective, randomized validation of the benefit of SRS awaits the results of the recently completed Radiation Therapy Oncology Group’s trial RTOG 93-05.

Tratamiento del dolor óseo metastásico con dosis repetidas de Estroncio-89 en pacientes con neoplasia de próstata

This study has aimed to evaluate the usefulness of repeated treatment with 89Sr in patients with prostate neoplasm and metastatic bone pain. Seventeen patients with partial or complete response after the first dose were retreated with two or more doses (total of 39 doses). The Karnofsky functional status, pain and degree of analgesia were assessed. After the first dose the response was good in 68% of the patients and partial in 32%. After the second dose, the response was good in 62% of the patients, partial in 15% and there was no response in 23% of the cases. The pre-treatment Karnofsky functional status and duration of the effect of 89Sr was lower after the second dose (p = 0.03, p = 0.02), but there were no statistically significant differences in the type of response. In conclusion, re-treatment with 89Sr can be administered safely and with a similar response to that achieved after the first dose.

The role of tumor resection in the treatment of glioblastoma multiforme in adults

The therapeutic impact of tumor resection is poorly defined. Therefore the current study was conducted. A retrospective, 2-institutional study was conducted (1991-1994) to compare the treatment results of stereotactic biopsy plus radiation therapy (99 patients; tumor dose: 60 gray [Gy]) with those of surgical resection plus radiation therapy (126 patients; tumor dose: 60 Gy). Only adult patients with supratentorial, lobar located, de novo glioblastoma were included. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the multivariate Cox proportional hazards model. Patients were categorized in the Radiation Therapy Oncology Group (RTOG) Classes IV (46 patients), V (157 patients), and VI (22 patients). The resection group and the biopsy group did not differ in terms of age, pretreatment Karnofsky performance status KPS), gender, duration of symptoms, presenting symptoms, tumor location, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have left-sided tumors (P < 0.001). Transient perioperative morbidity and mortality rates were 1% and 1%, respectively, in the biopsy group and 5% and 1.6%, respectively, in the resection group (P > 0.05). The median survival time was 37 weeks for the resection group and 33 weeks for the biopsy group. The difference was not statistically significant (P = 0.09). The most favorable pretreatment prognostic factor was patient age < 60 years (P < 0.01). Tumor resection was highly effective in patients with midline shift (P < 0.01). In patients without midline shift radiation therapy alone was found to be as effective as tumor resection plus radiation therapy (P = 0.5). Patients with midline shift were more likely to have a worse KPS during the course of primary radiation therapy (P < 0.05). For RTOG Classes IV-VI patients with moderate mass effect of the tumor, radiation therapy alone is a rational treatment strategy. Tumor resection should be performed in patients with pretreatment midline shift whenever possible.

Linear accelerator-based stereotaxic radiosurgery for brain metastases:the influence of number of lesions on survival.

To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment. Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses. The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume. Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.