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.     

Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome.

OBJECT: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. METHODS: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. CONCLUSIONS: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.     

Treatment of nasopharyngeal carcinoma: stereotactic radiosurgical boost following fractionated radiotherapy

Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.     

Case-control study of stereotactic radiosurgery for recurrent glioblastoma multiforme

OBJECT: The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma multiforme (GBM) was evaluated in a case-control study. METHODS: All patients who underwent SRS for recurrent GBM before March 2003 formed the case group. A control group of patients who did not undergo SRS was created from an institutional database, and each case was matched for known prognostic factors in GBM. The medical and neuroimaging records of all the patients were reviewed, and survival and treatment outcomes were recorded. The case and control groups were well matched with regard to demographics and pre-SRS interventions. In the control group, the date on which magnetic resonance imaging identified a recurrent lesion that would have been eligible for SRS was deemed the "SRS" date. The number of surgeries performed in the control group was statistically higher than that in the case group. The median duration of overall survival from diagnosis was 26 months in the case group and 23 months in the control group. From the date of SRS or "SRS", the median duration of survival was 11 months in the case group and 10 months in the control group, a difference that was not statistically significant. CONCLUSIONS: It appears that a subgroup of patients with GBMs has a higher than expected median survival duration despite the initial prognostic factors. In patients with localized recurrences, survival may be prolonged by applying aggressive local disease management by using either SRS or resection to equal advantage.     

Contemporary results of radical radiotherapy for bladder transitional cell carcinoma in a district general hospital with cancer-centre status

OBJECTIVE: To assess the current efficacy and safety of definitive external beam radiotherapy (EBRT) in the treatment of invasive bladder transitional cell carcinoma (TCC) in a district general hospital with cancer-centre status. PATIENTS AND METHODS: The case notes of all patients with bladder TCC undergoing EBRT with curative intent over an 8-year period (1988-95) were reviewed. Additional missing outcome data were collected. RESULTS: In all, 120 patients (109 men; median age 70 years, range 34-90) underwent radical EBRT (40-65 Gy; fraction median=20) over the 8-year period. Staging, as assessed by examination under anaesthesia and computed tomography, was T1 in 16%, T2 in 43%, T3 in 38% and T4 in 3%. In 96 patients (80%) the tumour was poorly differentiated (G3). The overall morbidity at 12 months was 12%; proctitis occurred in nine patients (8%) and cystitis in five (4%). Sixty-seven patients (59%) developed a local recurrence and in 36 (30%) this was invasive. The overall median survival was 60 months. Thirty-three patients underwent salvage cystectomy with a subsequent median survival of 12.5 months. CONCLUSION: Modern radical multifraction EBRT in invasive bladder TCC has a low morbidity, with an overall median survival of 5 years.     

Permanent iodine-125 interstitial radiation therapy in the treatment of non-glioblastoma multiforme high-grade gliomas

BACKGROUND: This study evaluates prognostic factors influencing survival outcomes for 60 patients with permanent iodine-125 implants in the primary treatment of non-glioblastoma multiforme (GBM) high-grade gliomas. METHODS: Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/h with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan-Meier method for univariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 34 patients received external radiation therapy (5,000-6,000 cGy) before the implant; 13 patients were implanted without additional external beam radiation, and 13 patients underwent external radiation therapy before implant placement. RESULTS: With a mean follow-up of 77.6 months (range 3.5-164 months), 1-, 3-, 5- and 10-year survival were 86.7% (+/-0.05%), 60% (+/-0.07%), 50% (+/-0.07%) and 45.7% (+/-0.7%), respectively. The median survival time was 57 months. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%) and brain abscess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky score and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location and preoperative Karnofsky score greater than 70. RPA classification was used to define this group of patients. In RPA classes I and II (n = 43), 1-year survival was 93%, while 3-, 5- and 10-year survival was 67.4, 60.5 and 55.5%, respectively, and median survival time was 91 months. In RPA class III (n = 7), 1-year survival was 71.4%, while 3- and 5-year survival was 42.9 and 28.6%, respectively, and median survival time was 47 months. In RPA class IV (n = 10), 1-year survival was 60%, while 3-, 5- and 10-year survival was 50, 22.2 and 11.1%, respectively, and median survival time was 37 months. CONCLUSION: Brachytherapy with permanent implant of 125I appears promising in the treatment of primary non-GBM malignant gliomas. It improved survival time and reduced the incidence of complications and provided good quality of life. In order to further confirm these results, multicenter randomized prospective studies are needed. RPA analysis is a valid tool to define prognostically distinct survival groups. In this study, 2-year survival and median survival time were improved in all prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with 125I implants. Further randomized studies with effective stratification are needed.     

Prognostic factors in patients treated with stereotactic image-guided robotic radiosurgery for brain metastases: a single-center retrospective analysis of 223 patients

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4–51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p?=?0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.     

Interstitial high-dose-rate brachytherapy combined with cervical dissection on head and neck cancer

BACKGROUND: The literature is scarce regarding the use of interstitial high-dose-rate brachytherapy (I-HDR) as adjuvant treatment of the cervical region, and most reports are focused on primary tumors of the mobile tongue and oropharynx. We evaluated the outcome and morbidity related to an institutional treatment policy, using I-HDR as the sole adjuvant treatment or in combination with external beam radiotherapy (EBRT) at the Departments of Radiation Oncology and Head and Neck Surgery, Hospital do Cancer, Sao Paulo, Brazil. METHODS: From October 1994 to December 2003, charts of 42 patients who had biopsy-proven cervical head and neck cancer, with a median follow-up of 36 months (range, 8-111 months), were reviewed. The median age of the patients was 55 years (range, 31-76 years), and the male/female ratio was 4.25:1.00. Thirty-five patients had previous irradiation with EBRT, with doses ranging from 30 Gy to 65 Gy (median, 52 Gy). The total dose of I-HDR ranged from 12 Gy to 48 Gy (median, 24 Gy), given in three to 14 fractions (median, 6 fractions) in 2 to 8 days (median, 4 days). RESULTS: The total treatment time ranged from 19 to 83 days (median, 35 days). The 5- and 8-year overall survival (OS) rates were 52.5% and 48.1%, respectively; and the relapse-free survival (RFS) rates were 48.5% and 38.1%, respectively. The only statistically significant prognostic factor for RFS and OS at 5 and 8 years was margin status (p = .0050). Four patients (9.5%) had late adverse side effects, such as local dehiscence (n = 2), local ulcer (n = 1), and extensive neck fibrosis (n = 1), not related to a higher dose to the skin or graft. CONCLUSION: These results suggest that I-HDR can be recommended in selected patients with first presentation lesions, local recurrences, or second primary carcinomas, even with a previous course of EBRT, but further studies are eagerly awaited to delineate the optimum schedule for this combination-treatment modality.     

Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.     

Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity

BACKGROUND: Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. METHODS: The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m(2) during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence-free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. RESULTS: Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan-Meier overall, disease-specific, and locoregional recurrence-free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. CONCLUSION: This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules.     

Posterior fossa metastases: aggressive treatment improves survival

BACKGROUND: Brain metastases are a leading cause of mortality and morbidity in patients with malignancies. Infratentorial location has been considered a negative prognostic factor. METHODS: This retrospective study evaluated patients with cerebellar metastasis. Statistical analysis assessed age, extracranial disease, performance status and treatment. Patients were categorized by Radiation Therapy Oncology Group recursive partitioning analysis (RPA). Treatment included surgery, stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) alone or in combination. RESULTS: Of 93 patients, the median survival was 12.9 months for RPA class I, 11 months for class II and 8 months for class III. On multivariate analysis, RPA class was an important predictor for overall survival. However, SRS with WBRT or surgery with WBRT or a combination of SRS, surgery and WBRT, was more favorable than surgery or SRS alone within RPA class II patients. CONCLUSIONS: Survival of patients with cerebellar brain metastasis is comparable to that of patients with supratentorial brain metastasis using RPA classification. Aggressive multimodality therapy has a favorable impact on survival.     

Encouraging experience of concomitant Temozolomide with radiotherapy followed by adjuvant Temozolomide in newly diagnosed glioblastoma multiforme: single institution experience

The purpose of this study was to report our experience with concomitant and adjuvant temozolomide (TMZ) with radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Forty-two newly diagnosed histopathologically proven patients with GBM underwent maximal safe resection followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks along with concomitant oral TMZ (75 mg/m2) daily followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Patients were 13-69 years of age with a median age of 49.5 years (31 males, 11 females). Fifty per cent of patients underwent a gross total resection of tumour, 43% had partial resection, and 7% an open or stereotactic biopsy only. 53% of the patients had a post-operative Karnofsky Performance Score (KPS) of 60-80%. All patients received concomitant radiation and TMZ with 74% of the patients completing six cycles of adjuvant TMZ. At a median follow-up of 12.5 months, the 1- and 2-year survival was 67 and 29%, respectively. The median overall and progression-free survival was 16.4 and 14.9 months respectively. Patients with pretreatment KPS of >80% had significantly better overall survival as compared with those having KPS相似文献   

The effect of radiosurgery during management of aggressive meningiomas

BACKGROUND: Aggressive (atypical or malignant) meningiomas are difficult tumors to manage. We review the local control and survival rates of patients with aggressive meningiomas after multi-modality therapy that included stereotactic radiosurgery (SRS). METHODS: Thirty patients had SRS for treatment of malignant (n = 12) or atypical (n = 18) meningiomas. There were 17 (57%) males and 13 (43%) females with an average age of 58 years. The mean number of prior surgical resections was two. The median imaging follow-up was 2.3 (0.1-11.4) years; median clinical follow-up was 3.8 (0.25-11.5) years. RESULTS: After SRS, the overall median time until progression of neurologic signs was 48.0 (+/-6.51) months. Median time to neurologic progression was significantly worse for patients treated late after recurrence versus early after craniotomy. Atypical meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-13), while malignant meningiomas had 5- and 10-year overall actuarial survival rates of 59% (+/-16) and 0%. These curves were not significantly different from one another. Atypical meningiomas had a 5-year progression-free survival (PFS) of 83% (+/-7%), while malignant meningiomas had a 5-year PFS of 72% (+/-10) (p = 0.018). On multivariate analysis, early SRS and smaller tumor volumes were associated with better PFS, while younger age was associated with better survival. One patient had an adverse radiation effect after SRS. CONCLUSIONS: Stereotactic radiosurgery is an important adjuvant management strategy for residual tumors identified early after craniotomy and partial resection. Aggressive use of early boost radiosurgery following craniotomy and radiation therapy is recommended for patients with malignant meningiomas.     

Late urinary morbidity with high dose prostate brachytherapy as a boost to conventional external beam radiation therapy for local and locally advanced prostate cancer

PURPOSE: Late urinary retention (UR) is a known complication that may occur when using high dose rate brachytherapy (HDR-B) to boost external beam radiation therapy (EBRT) when treating prostate cancer. However, the dosimetric, treatment and clinical factors associated with this complication are not well-known. MATERIALS AND METHODS: From March 1997 to March 2000 a total of 108 patients with local or locally advanced prostate adenocarcinoma were treated with EBRT (45 Gy) and HDR-B as a boost, when 16 to 20 Gy was given in 4 fractions twice daily. Median patient age was 68 years and median followup was 44 months (range 36 to 72). Each implant was performed using 8 to 18 needles with a median active length of 3 cm. Planning ultrasound target volume ranged from 23 to 65 cc. RESULTS: Biological effective doses for the urethral region ranged from 107 to 138 Gy3 (median 113). Crude and 5-year actuarial UR-free survival were 95.4% and 86.2%, respectively. Predictive factors for UR on univariate analysis were age more than 65 years (p = 0.0416), planning ultrasound target volume greater than 35 cc and active length of needles more than 3.5 cm (p = 0.0158). On multivariate analysis by Cox regression age was the only predictive factor (p = 0.027). CONCLUSIONS: HDR-B appears to offer a safe, reproducible and effective method of boosting conventional EBRT in patients with locally advanced prostate cancer. Results with this technology reveal late urinary morbidity rates paralleling those achieved with other forms of treatment, but further long-term followup is still needed to warrant a definitive conclusion.     

Stereotactic radiosurgery for pituitary metastases

Background

We evaluated the role of Gamma Knife SRS in the multidisciplinary management of metastatic cancer to the pituitary gland.

Methods

We retrospectively reviewed records of 18 consecutive pituitary metastasis patients who underwent Gamma Knife SRS during a 21-year experience. The median patient age was 57.6 years (range, 27.0-81.1 years). There were 5 patients who had initial surgical resection of their pituitary metastasis, 5 who had fractionated radiation, and 7 who had CT before SRS. The median radiosurgery target volume was 3.5 mL (range, 0.2-18.0 mL), and the median marginal dose was 13.0 Gy (range, 9-18 Gy).

Results

The overall survival after SRS at 3, 6, and 12 months, respectively, was 66%, 36%, and 18%. The median survival after SRS was 5.2 months. The progression-free survival after SRS was 100% and 66.7% at 6 and 12 months, respectively. The only factor associated with an improved overall survival was younger age at presentation. Diabetes insipidus improved in 3 (42.9%) of 7 patients. Neurological symptoms or signs improved in 4 (50.0%) of 8 patients. Three (16.7%) patients developed new neurological deficits due to tumor progression despite SRS.

Conclusion

Development of a pituitary metastasis is an ominous finding in the context of systemic cancer. Stereotactic radiosurgery is an effective palliative approach for most patients with pituitary metastasis.     

Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy

BACKGROUND: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy. METHODS: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively. RESULTS: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths. CONCLUSIONS: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma.     

Resection of brain metastases previously treated with stereotactic radiosurgery

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.     

Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group

OBJECT: This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.     

Influence of Resection Margins on Survival for Patients With Pancreatic Cancer Treated by Adjuvant Chemoradiation and/or Chemotherapy in the ESPAC-1 Randomized Controlled Trial

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.     

Adjuvant intraoperative electron radiotherapy and external beam radiotherapy for locally advanced transitional cell carcinoma of the ureter

ObjectiveSurgery is the mainstay treatment for transitional cell carcinoma (TCC) of the ureter; however, local recurrence remains a common cause of treatment failure for locally advanced disease after surgery, and the benefit of adjuvant radiotherapy has not been completely determined. The objective of this analysis was to evaluate the outcome of postsurgical high dose radiotherapy consisting of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in locally advanced transitional cell carcinoma of the ureter.MethodsSeventeen patients with pathologically diagnosed TCC of ureter were treated with nephroureterectomy and adjuvant radiation consisted of IOERT and EBRT according to an institutional research protocol. The dose of IOERT ranged between 10 to 20 Gy (median 14 Gy). Conventional EBRT given with the total dose ranged between 36 and 45 Gy (median 42 Gy). Chemotherapy was utilized in 10 of the 17 patients at the discretion of their primary oncologist.ResultsThe median follow-up for all patients was 48 months (range, 10–91 months). The overall survivals of the entire group of patients at 1, 3, and 5 years were 82%, 65%, and 46%, respectively. The estimated locoregional control rates at 1, 3, and 5 year were 82%, 64%, and 51%, respectively. Depth of invasion (pT), histological grade, and presence of residual disease were significant prognostic factors in univariate analysis. Multivariate analysis revealed that independent prognostic factors for survival included histological grade (grade 1 + 2 vs. grade 3 + 4; P = 0.03) and presence of residual disease after surgery (R0 vs. R1 or R2 resection; P = 0.053). Acute and long-term adverse effects rated grade 3 or higher were seen in 4 and 2 patients, respectively. No grade 5 toxicity occurred.ConclusionIOERT and EBRT following surgery produced a 51% local control and 46% overall survival rate for locally advanced TCC of ureter at 5 years of follow-up, with acceptable rates of acute and late toxicity. Adjuvant IOERT appears to permit dose escalation safely in patients who received conventional adjuvant EBRT and chemotherapy. This strategy deserves to be optimized and then tested in a prospective trial to learn if it can further improve outcome.