Nadia Laack - Academia.edu (original) (raw)

Papers by Nadia Laack

JCO Global Oncology, 2021

We hope to add clarification to the authors’ interpretation of RTOG 0614. Although it is true tha... more We hope to add clarification to the authors’ interpretation of RTOG 0614. Although it is true that statistical significance was not reached at 24 weeks (P = .059) for decline in delayed recall, it is important to note that only 149 of 554 patients were analyzable at that time point, resulting in 35% statistical power to detect an absolute 0.87 difference. Additionally, the authors describe a small decline in delayed recall in the memantine arm at 24 weeks, although in actuality the patients on the memantine arm did not demonstrate cognitive decline on the Hopkins Verbal Learning TestRevised (HVLT-R) Delayed Recognition (median decline of 0) compared with the placebo arm (median decline of −0.90) at 24 weeks.

The Lancet Oncology, 2017

Background Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial contro... more Background Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. Methods In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5•0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37•5 Gy in 15 daily fractions of 2•5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Findings Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11•1 months (IQR 5•1-18•0). Cognitive-deteriorationfree survival was longer in patients assigned to SRS (median 3•7 months [95% CI 3•45-5•06], 93 events) than in patients assigned to WBRT (median 3•0 months [2•86-3•25], 93 events; hazard ratio [HR] 0•47 [95% CI 0•35-0•63]; p<0•0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference-33•6% [95% CI-45•3 to-21•8], p<0•00031). Median overall survival was 12•2 months (95% CI 9•7-16•0, 69 deaths) for SRS and 11•6 months (9•9-18•0, 67 deaths) for WBRT (HR 1•07 [95% CI 0•76-1•50]; p=0•70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Interpretation Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. Funding National Cancer Institute.

Advances in Radiation Oncology, 2016

Background: Spine stereotactic body radiation therapy (SBRT) is becoming widely accepted as first... more Background: Spine stereotactic body radiation therapy (SBRT) is becoming widely accepted as first-line treatment of oligometastatic spine disease as well as in the postoperative setting. The reported incidence of myelopathy is very low and guidelines vary widely on the maximum tolerable dose of the spinal cord and thecal sac. Methods and materials: Between April 2008 and December 2010, radiation parameters were exported for 46 patients treated with spine SBRT at the Mayo Clinic. Using an in-house data mining program, dose-volume histogram constraints were extracted, including dose prescription, dose fractionation, planning target volume, planning target volume coverage, maximum dose to the cord, D2cc thecal sac, and D2cc spinal cord. Diagnostic magnetic resonance imaging scans and/or computed tomography myelograms were fused with the planning set to delineate the cord and thecal sac for receiver operating characteristic analysis of cord and thecal sac subvolume doses. A high-resolution planning at-risk volume was created in 1-mm increments for cord (1-7 mm) and the thecal sac (1-2 mm) to examine dose gradients that might be correlated with toxicity. Results: No patients experienced myelopathy with a median follow-up of 14 months. The most common toxicities were pain and nausea. Median values of D2cc maximum dose (maximum dose received by 2 cc of the organ at risk; biologically equivalent 2-Gy dose maximum [EQD2]) for cord and thecal sac were 38.5 Gy (range, 7.5-67.9 Gy) and 67.7 Gy (range, 15.5-155.8 Gy), respectively. Median values for high-dose subvolumes for cord and thecal sac were 2 times higher than the doses for 5% predicted grade 3 cord toxicity as recommended in the current literature. Cord D0.1cc[EQD2] !23.8 Gy was correlated with pain flare (n Z 5). Thecal sac D2cc [EQD2] !29.3 Gy was a significant indicator of nausea. Conclusion: Current guidelines may overestimate the risk of myelopathy from spine SBRT. The current study's population included both radiation-naïve and retreatment cases, but no myelopathy was observed despite exceeding recommended spine limits.

Radiotherapy and Oncology, 2015

S730 3rd ESTRO Forum 2015 research project as clinical data, imaging features and quality of life... more S730 3rd ESTRO Forum 2015 research project as clinical data, imaging features and quality of life evaluation. Conclusions: The creation of a formal ontology is the starting point to share and collect data from multiple datasets. It allows to obtain a clear and a common interpretation of concepts, to report information in standardized large database. Along these lines the multi-professional team has in use a suitable support to implement decision support system based on predictive models. EP-1354 Impact of evaluation timing in determining patterns of failure in glioblastoma

Seminars in Radiation Oncology, 2015

Treatment of newly diagnosed or suspected low-grade glioma (LGG) is one of the most controversial... more Treatment of newly diagnosed or suspected low-grade glioma (LGG) is one of the most controversial areas in neuro-oncology. The heterogeneity of these tumors, concern regarding morbidity of treatment, and absence of proven overall survival benefit from any known treatment have resulted in a lack of consensus regarding the timing and extent of surgery, timing of radiotherapy (RT), and role of chemotherapy. The long-term results of Radiation Therapy Oncology Group (RTOG) 9802, a phase III randomized trial comparing RT alone with RT and 6 cycles of adjuvant procarbazine, CCNU, vincristine (PCV), demonstrated an unprecedented 5.5year improvement in median overall survival with the addition of PCV chemotherapy in high-risk patients with LGG. These results are practice changing and define a new standard of care for these patients. However, in the intervening decade since the trial was completed, novel molecular markers as well as newer chemotherapy agents such as temozolomide have been developed, which make these results difficult to incorporate into clinical practice. This review summarizes the evidence for and against the role of upfront RT and PCV in newly diagnosed patients with LGG.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2015

A primary brain tumor patient and caregiver survey was completed to investigate interest in brief... more A primary brain tumor patient and caregiver survey was completed to investigate interest in brief support opportunities, focused on education, memory training, and healthy coping, during a routine clinical visit and at 3-month follow-up. Patients with primary brain tumors receiving care in the Radiation Oncology Department at Mayo Clinic Rochester and their caregivers were recruited to complete the survey between June 2008 and September 2009. Both patients and their caregivers expressed greatest interest in education about brain tumors and cognitive effects of treatment. Interest in support opportunities targeting education, memory training, or healthy coping was low to modest. Bimodal distributions were found for almost all the support opportunities, revealing subgroups of patients and caregivers with high interest in such sessions. Overall, ratings of interest did not differ over time. Patients with primary brain tumors and their caregivers expressed most interest in education abo...

Journal of Neuro-Oncology, 2015

The utility of current response criteria has not been established in anaplastic astrocytoma (AA).... more The utility of current response criteria has not been established in anaplastic astrocytoma (AA). We retrospectively reviewed MR images for 20 patients with AA and compared RANO-based approaches to clinician impression described as follow: (1) standard RANO-based criteria met by growth of or development of new enhancing lesion (RANO-C), (2) RANO criteria for progression based on significant FLAIR increase (RANO-F) and (3) clinical progression usually resulting in change of treatment (Clinical). Patterns of failure (POF) were analyzed utilizing all proposed progression MRIs fused with the patients' radiotherapy treatment plan. With an overall median survival of 24.3 months, development of new enhancing lesion was the most common determinant of progression (70 % of patients). Median time to RANO-C, RANO-F and Clinical progression

Radiation Oncology, 2012

Over the past 20 years, several proton beam treatment programs have been implemented throughout t... more Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence: Proton beam therapy is a technically advanced and promising form of radiation therapy.

Neuro-Oncology, 2009

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-gr... more The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month-38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free

Neuro-Oncology, 2013

Background. To identify changes in patient presentation, treatment, and outcomes of low-grade gli... more Background. To identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years. Methods. Records of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960-1989) and after (group II: 1990-2011) the routine use of postoperative MRI. Results. Median follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/ motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P , .0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/ rSTR. Conclusions. OS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients.

Mayo Clinic Proceedings, 2012

Osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the most common malignant musculoskeletal t... more Osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the most common malignant musculoskeletal tumors in children and adolescents. Today, most patients can be cured. Numerous factors have contributed to improved outcome for these patients over the past several decades. These include multidisciplinary care involving oncologists, radiation oncologists, surgeons, pathologists, and radiologists and enrollment of patients in clinical trials. Better understanding of molecular mechanisms of disease have resulted in studies using molecular targets in addition to standard chemotherapeutic agents, which hopefully will lead to better outcomes in the future. Moreover, new orthopedic techniques and devices as well as new technologies in radiation oncology hold promise for better local control of primary tumors and the potential for fewer late adverse effects. Despite this progress, patients must undergo lifelong follow-up for possible late effects of intense chemotherapy and radiation therapy. We review the diagnosis, prognosis, staging, multidisciplinary therapy, new directions in therapy, and long-term complications of treatment for these tumors. For this review, we searched MEDLINE using the terms rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, biology, and humans and limited the search to articles from 2000 to September 2011. Additional references found in these articles were utilized as appropriate, as well as references from the background information in current therapeutic studies of the Children's Oncology Group. The same database and time frame were searched for articles written by leading authorities in the field.

Journal of Pediatric Hematology/Oncology, 2013

This study reports changes in long-term survival after the introduction of modern imaging in pedi... more This study reports changes in long-term survival after the introduction of modern imaging in pediatric patients with low-grade gliomas (LGGs). Records from 351 consecutive pediatric patients diagnosed with LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009) postoperative magnetic resonance imaging became regularly used in pediatric LGG. Median progression-free survival (PFS) and overall survival (OS) were not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate analysis, improved PFS was associated with gross total resection (GTR; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and postoperative radiation therapy (RT; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). In those undergoing less than GTR, PFS was improved with RT, nearing rates of patients receiving GTR (P=0.12). On multivariate analysis, higher OS was associated with GTR (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and pilocytic histology (P=0.03). Group II had fewer headaches, fewer sensory/motor symptoms, less postoperative RT, and more GTRs. OS and PFS were not different between the groups. This large series of pediatric LGG patients with long-term follow-up found no significant changes in OS or PFS over time. Overall, GTR was associated with improved OS and PFS. RT was associated with an improvement in PFS, with the greatest benefit seen in patients undergoing less than GTR.

Journal of Neuro-Oncology, 2012

Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of pati... more 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 ϭ 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P ϭ 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 ϭ 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 ϭ 0.038) and histological diagnosis of primary tumor (P Ͻ 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 ϭ 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 ϭ 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.

International Journal of Radiation Oncology*Biology*Physics, 2012

International Journal of Radiation Oncology*Biology*Physics, 2012

Prior studies suggest that providers and patients may be overly optimistic when predicting progno... more Prior studies suggest that providers and patients may be overly optimistic when predicting prognosis for incurable cancers. This may lead to unnecessarily aggressive therapies near the end of life, such as lengthy courses of palliative RT. We investigated patient beliefs and understanding about the goals of palliative RT for incurable lung cancers. Materials/Methods: The Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study, a population-and health system-based prospective cohort study, enrolled 5,013 patients with newly diagnosed lung cancer in 5 geographic regions, 10 Veterans Administration sites, and 5 large health maintenance organizations from 2003-2005. We identified patients age 21 with stage IIIB (wet) or IV lung cancer who completed or were scheduled to have RT and completed the baseline interview approximately 4 months after diagnosis. We analyzed patient/surrogate responses to the question: "After talking with your doctors about radiation therapy, how likely did you think it was that radiation would." Results: Among 832 patients with stage IIIB or IV lung cancer at diagnosis who had received or were scheduled to have RT, 384 (46%) completed surveys on their beliefs about RT. Median survival in this cohort was 11.5 months. 78% of patients believed that RT was very or somewhat likely to help them live longer, and 43% believed that RT was very or somewhat likely to cure their cancer. With respect to symptoms, 67% believed that RT was very or somewhat likely help them with problems they were having because of lung cancer, and 66% believed that RT was very or somewhat likely to have side effects or complications. Full results are shown in the Table. Conclusions: A majority of patients with incurable lung cancer who receive palliative radiation believe that it is likely to prolong life, and a significant proportion believes that it is likely to cure their disease. This suggests an opportunity to improve care delivery by improving patient communication and understanding of the goals of palliative RT.

International Journal of Radiation Oncology*Biology*Physics, 2013

conformality number (CN) and heterogeneity index (HI) of the target was determined for each plan,... more conformality number (CN) and heterogeneity index (HI) of the target was determined for each plan, and two tail student paired t-test was used to compare differences in the mean for each parameter. The importance of tumor factors (volume, location), patient factors (FEV1 or Functional Expiratory Volume in 1 second, body mass index) and treatment factors (number of SBRT beams) on the dose distributions obtained from the two algorithms, were statistically determined using linear regression analyses. Results: No difference to mean target dose was observed for the plans from either algorithm. However, in comparison to AAA, a small and significant difference in dose distribution (p < 0.00001) to the target was found for the Acuros XB algorithm, resulting in lower conformity (-2.1%, p < 0.00001) and higher heterogeneity of dose. Single logistic regression identified FEV1, number of beams and target location as having a strong correlation with the difference of CN between the two calculations. Multivariable analysis indicated that FEV1 (p Z 0.0296) was the only predictor for the difference seen in the two dose calculation algorithms. Conclusions: Although no difference in mean target dose was identified between Acuros XB and AAA; there is a small, but significant difference in target dose distribution. This leads to differences in target dose conformality and heterogeneity for this cohort of patients. The patients' lung function, which leads to changes in the lung density, correlates with the degree of difference in conformality between the two dose calculation algorithms. The reason for this difference is secondary to the accurate modeling of tissue by the Acuros XB algorithm. The current study supports that the Acuros XB algorithm is a more suitable tool for dose calculation in patients with poor pulmonary function, than the convolution based algorithm.

International Journal of Radiation Oncology*Biology*Physics, 2013

International Journal of Radiation Oncology*Biology*Physics, 2011

Purpose-To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxor... more Purpose-To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials-Patients 70 years old and younger with newly diagnosed, biopsyproven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival.

International Journal of Radiation Oncology*Biology*Physics, 2007

old. Sixteen patients had a GTR, 13 had a STR, 2 patients had a surgical resection but the extent... more old. Sixteen patients had a GTR, 13 had a STR, 2 patients had a surgical resection but the extent of tumor removal was not known and 3 patients did not undergo a surgical resection. Histology was unfavorable in 23, favorable in 4 and unknown in 7 patients. Eleven patients were found to have n-myc amplification, 17 did not, and n-myc status was unknown in 6 patients. Two patients received TBI in preparation for tandem transplantation. The majority of patients had a tandem transplant. The average time from last transplant to the start of local RT was 66.6 days (range 41-136 days). Median radiation dose was 23.2 (range 12-30 Gy, including TBI dose, when applicable). The median dose delivered to patients following a STR was 23.8 Gy. The majority of patients received conventional RT, 6 patients received IMRT. The majority of patients received adjuvant cis-retinoic acid. Results: At the time of analysis 3 patients died of disease, 5 patients were alive with disease, 23 patients were in clinical remission and 3 patients were lost to follow-up. No patients demonstrated failure at the primary tumor site at the time of disease progression. All relapses were distant. Five year Actuarial Overall Survival was 87%. Conclusions: Radiation therapy plays an important role in the local control of neuroblastoma. Our institution has achieved excellent local control in high-risk neuroblastoma patients regardless of resection status. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for both GTR and STR patients in the setting of tandem transplantation and maintenance therapy.

International Journal of Radiation Oncology*Biology*Physics, 2006

The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radioth... more The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapytreated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p ‫؍‬ 0.76) and EFS (11.7 vs. 4.0 months, p ‫؍‬ 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.

JCO Global Oncology, 2021

We hope to add clarification to the authors’ interpretation of RTOG 0614. Although it is true tha... more We hope to add clarification to the authors’ interpretation of RTOG 0614. Although it is true that statistical significance was not reached at 24 weeks (P = .059) for decline in delayed recall, it is important to note that only 149 of 554 patients were analyzable at that time point, resulting in 35% statistical power to detect an absolute 0.87 difference. Additionally, the authors describe a small decline in delayed recall in the memantine arm at 24 weeks, although in actuality the patients on the memantine arm did not demonstrate cognitive decline on the Hopkins Verbal Learning TestRevised (HVLT-R) Delayed Recognition (median decline of 0) compared with the placebo arm (median decline of −0.90) at 24 weeks.

The Lancet Oncology, 2017

Background Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial contro... more Background Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. Methods In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5•0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37•5 Gy in 15 daily fractions of 2•5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Findings Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11•1 months (IQR 5•1-18•0). Cognitive-deteriorationfree survival was longer in patients assigned to SRS (median 3•7 months [95% CI 3•45-5•06], 93 events) than in patients assigned to WBRT (median 3•0 months [2•86-3•25], 93 events; hazard ratio [HR] 0•47 [95% CI 0•35-0•63]; p<0•0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference-33•6% [95% CI-45•3 to-21•8], p<0•00031). Median overall survival was 12•2 months (95% CI 9•7-16•0, 69 deaths) for SRS and 11•6 months (9•9-18•0, 67 deaths) for WBRT (HR 1•07 [95% CI 0•76-1•50]; p=0•70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Interpretation Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. Funding National Cancer Institute.

Advances in Radiation Oncology, 2016

Background: Spine stereotactic body radiation therapy (SBRT) is becoming widely accepted as first... more Background: Spine stereotactic body radiation therapy (SBRT) is becoming widely accepted as first-line treatment of oligometastatic spine disease as well as in the postoperative setting. The reported incidence of myelopathy is very low and guidelines vary widely on the maximum tolerable dose of the spinal cord and thecal sac. Methods and materials: Between April 2008 and December 2010, radiation parameters were exported for 46 patients treated with spine SBRT at the Mayo Clinic. Using an in-house data mining program, dose-volume histogram constraints were extracted, including dose prescription, dose fractionation, planning target volume, planning target volume coverage, maximum dose to the cord, D2cc thecal sac, and D2cc spinal cord. Diagnostic magnetic resonance imaging scans and/or computed tomography myelograms were fused with the planning set to delineate the cord and thecal sac for receiver operating characteristic analysis of cord and thecal sac subvolume doses. A high-resolution planning at-risk volume was created in 1-mm increments for cord (1-7 mm) and the thecal sac (1-2 mm) to examine dose gradients that might be correlated with toxicity. Results: No patients experienced myelopathy with a median follow-up of 14 months. The most common toxicities were pain and nausea. Median values of D2cc maximum dose (maximum dose received by 2 cc of the organ at risk; biologically equivalent 2-Gy dose maximum [EQD2]) for cord and thecal sac were 38.5 Gy (range, 7.5-67.9 Gy) and 67.7 Gy (range, 15.5-155.8 Gy), respectively. Median values for high-dose subvolumes for cord and thecal sac were 2 times higher than the doses for 5% predicted grade 3 cord toxicity as recommended in the current literature. Cord D0.1cc[EQD2] !23.8 Gy was correlated with pain flare (n Z 5). Thecal sac D2cc [EQD2] !29.3 Gy was a significant indicator of nausea. Conclusion: Current guidelines may overestimate the risk of myelopathy from spine SBRT. The current study's population included both radiation-naïve and retreatment cases, but no myelopathy was observed despite exceeding recommended spine limits.

Radiotherapy and Oncology, 2015

S730 3rd ESTRO Forum 2015 research project as clinical data, imaging features and quality of life... more S730 3rd ESTRO Forum 2015 research project as clinical data, imaging features and quality of life evaluation. Conclusions: The creation of a formal ontology is the starting point to share and collect data from multiple datasets. It allows to obtain a clear and a common interpretation of concepts, to report information in standardized large database. Along these lines the multi-professional team has in use a suitable support to implement decision support system based on predictive models. EP-1354 Impact of evaluation timing in determining patterns of failure in glioblastoma

Seminars in Radiation Oncology, 2015

Treatment of newly diagnosed or suspected low-grade glioma (LGG) is one of the most controversial... more Treatment of newly diagnosed or suspected low-grade glioma (LGG) is one of the most controversial areas in neuro-oncology. The heterogeneity of these tumors, concern regarding morbidity of treatment, and absence of proven overall survival benefit from any known treatment have resulted in a lack of consensus regarding the timing and extent of surgery, timing of radiotherapy (RT), and role of chemotherapy. The long-term results of Radiation Therapy Oncology Group (RTOG) 9802, a phase III randomized trial comparing RT alone with RT and 6 cycles of adjuvant procarbazine, CCNU, vincristine (PCV), demonstrated an unprecedented 5.5year improvement in median overall survival with the addition of PCV chemotherapy in high-risk patients with LGG. These results are practice changing and define a new standard of care for these patients. However, in the intervening decade since the trial was completed, novel molecular markers as well as newer chemotherapy agents such as temozolomide have been developed, which make these results difficult to incorporate into clinical practice. This review summarizes the evidence for and against the role of upfront RT and PCV in newly diagnosed patients with LGG.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2015

A primary brain tumor patient and caregiver survey was completed to investigate interest in brief... more A primary brain tumor patient and caregiver survey was completed to investigate interest in brief support opportunities, focused on education, memory training, and healthy coping, during a routine clinical visit and at 3-month follow-up. Patients with primary brain tumors receiving care in the Radiation Oncology Department at Mayo Clinic Rochester and their caregivers were recruited to complete the survey between June 2008 and September 2009. Both patients and their caregivers expressed greatest interest in education about brain tumors and cognitive effects of treatment. Interest in support opportunities targeting education, memory training, or healthy coping was low to modest. Bimodal distributions were found for almost all the support opportunities, revealing subgroups of patients and caregivers with high interest in such sessions. Overall, ratings of interest did not differ over time. Patients with primary brain tumors and their caregivers expressed most interest in education abo...

Journal of Neuro-Oncology, 2015

The utility of current response criteria has not been established in anaplastic astrocytoma (AA).... more The utility of current response criteria has not been established in anaplastic astrocytoma (AA). We retrospectively reviewed MR images for 20 patients with AA and compared RANO-based approaches to clinician impression described as follow: (1) standard RANO-based criteria met by growth of or development of new enhancing lesion (RANO-C), (2) RANO criteria for progression based on significant FLAIR increase (RANO-F) and (3) clinical progression usually resulting in change of treatment (Clinical). Patterns of failure (POF) were analyzed utilizing all proposed progression MRIs fused with the patients' radiotherapy treatment plan. With an overall median survival of 24.3 months, development of new enhancing lesion was the most common determinant of progression (70 % of patients). Median time to RANO-C, RANO-F and Clinical progression

Radiation Oncology, 2012

Over the past 20 years, several proton beam treatment programs have been implemented throughout t... more Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence: Proton beam therapy is a technically advanced and promising form of radiation therapy.

Neuro-Oncology, 2009

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-gr... more The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month-38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free

Neuro-Oncology, 2013

Background. To identify changes in patient presentation, treatment, and outcomes of low-grade gli... more Background. To identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years. Methods. Records of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960-1989) and after (group II: 1990-2011) the routine use of postoperative MRI. Results. Median follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/ motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P , .0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/ rSTR. Conclusions. OS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients.

Mayo Clinic Proceedings, 2012

Osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the most common malignant musculoskeletal t... more Osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the most common malignant musculoskeletal tumors in children and adolescents. Today, most patients can be cured. Numerous factors have contributed to improved outcome for these patients over the past several decades. These include multidisciplinary care involving oncologists, radiation oncologists, surgeons, pathologists, and radiologists and enrollment of patients in clinical trials. Better understanding of molecular mechanisms of disease have resulted in studies using molecular targets in addition to standard chemotherapeutic agents, which hopefully will lead to better outcomes in the future. Moreover, new orthopedic techniques and devices as well as new technologies in radiation oncology hold promise for better local control of primary tumors and the potential for fewer late adverse effects. Despite this progress, patients must undergo lifelong follow-up for possible late effects of intense chemotherapy and radiation therapy. We review the diagnosis, prognosis, staging, multidisciplinary therapy, new directions in therapy, and long-term complications of treatment for these tumors. For this review, we searched MEDLINE using the terms rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, biology, and humans and limited the search to articles from 2000 to September 2011. Additional references found in these articles were utilized as appropriate, as well as references from the background information in current therapeutic studies of the Children's Oncology Group. The same database and time frame were searched for articles written by leading authorities in the field.

Journal of Pediatric Hematology/Oncology, 2013

This study reports changes in long-term survival after the introduction of modern imaging in pedi... more This study reports changes in long-term survival after the introduction of modern imaging in pediatric patients with low-grade gliomas (LGGs). Records from 351 consecutive pediatric patients diagnosed with LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009) postoperative magnetic resonance imaging became regularly used in pediatric LGG. Median progression-free survival (PFS) and overall survival (OS) were not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate analysis, improved PFS was associated with gross total resection (GTR; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and postoperative radiation therapy (RT; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). In those undergoing less than GTR, PFS was improved with RT, nearing rates of patients receiving GTR (P=0.12). On multivariate analysis, higher OS was associated with GTR (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and pilocytic histology (P=0.03). Group II had fewer headaches, fewer sensory/motor symptoms, less postoperative RT, and more GTRs. OS and PFS were not different between the groups. This large series of pediatric LGG patients with long-term follow-up found no significant changes in OS or PFS over time. Overall, GTR was associated with improved OS and PFS. RT was associated with an improvement in PFS, with the greatest benefit seen in patients undergoing less than GTR.

Journal of Neuro-Oncology, 2012

Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of pati... more 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 ϭ 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P ϭ 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 ϭ 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 ϭ 0.038) and histological diagnosis of primary tumor (P Ͻ 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 ϭ 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 ϭ 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.

International Journal of Radiation Oncology*Biology*Physics, 2012

International Journal of Radiation Oncology*Biology*Physics, 2012

Prior studies suggest that providers and patients may be overly optimistic when predicting progno... more Prior studies suggest that providers and patients may be overly optimistic when predicting prognosis for incurable cancers. This may lead to unnecessarily aggressive therapies near the end of life, such as lengthy courses of palliative RT. We investigated patient beliefs and understanding about the goals of palliative RT for incurable lung cancers. Materials/Methods: The Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study, a population-and health system-based prospective cohort study, enrolled 5,013 patients with newly diagnosed lung cancer in 5 geographic regions, 10 Veterans Administration sites, and 5 large health maintenance organizations from 2003-2005. We identified patients age 21 with stage IIIB (wet) or IV lung cancer who completed or were scheduled to have RT and completed the baseline interview approximately 4 months after diagnosis. We analyzed patient/surrogate responses to the question: "After talking with your doctors about radiation therapy, how likely did you think it was that radiation would." Results: Among 832 patients with stage IIIB or IV lung cancer at diagnosis who had received or were scheduled to have RT, 384 (46%) completed surveys on their beliefs about RT. Median survival in this cohort was 11.5 months. 78% of patients believed that RT was very or somewhat likely to help them live longer, and 43% believed that RT was very or somewhat likely to cure their cancer. With respect to symptoms, 67% believed that RT was very or somewhat likely help them with problems they were having because of lung cancer, and 66% believed that RT was very or somewhat likely to have side effects or complications. Full results are shown in the Table. Conclusions: A majority of patients with incurable lung cancer who receive palliative radiation believe that it is likely to prolong life, and a significant proportion believes that it is likely to cure their disease. This suggests an opportunity to improve care delivery by improving patient communication and understanding of the goals of palliative RT.

International Journal of Radiation Oncology*Biology*Physics, 2013

conformality number (CN) and heterogeneity index (HI) of the target was determined for each plan,... more conformality number (CN) and heterogeneity index (HI) of the target was determined for each plan, and two tail student paired t-test was used to compare differences in the mean for each parameter. The importance of tumor factors (volume, location), patient factors (FEV1 or Functional Expiratory Volume in 1 second, body mass index) and treatment factors (number of SBRT beams) on the dose distributions obtained from the two algorithms, were statistically determined using linear regression analyses. Results: No difference to mean target dose was observed for the plans from either algorithm. However, in comparison to AAA, a small and significant difference in dose distribution (p < 0.00001) to the target was found for the Acuros XB algorithm, resulting in lower conformity (-2.1%, p < 0.00001) and higher heterogeneity of dose. Single logistic regression identified FEV1, number of beams and target location as having a strong correlation with the difference of CN between the two calculations. Multivariable analysis indicated that FEV1 (p Z 0.0296) was the only predictor for the difference seen in the two dose calculation algorithms. Conclusions: Although no difference in mean target dose was identified between Acuros XB and AAA; there is a small, but significant difference in target dose distribution. This leads to differences in target dose conformality and heterogeneity for this cohort of patients. The patients' lung function, which leads to changes in the lung density, correlates with the degree of difference in conformality between the two dose calculation algorithms. The reason for this difference is secondary to the accurate modeling of tissue by the Acuros XB algorithm. The current study supports that the Acuros XB algorithm is a more suitable tool for dose calculation in patients with poor pulmonary function, than the convolution based algorithm.

International Journal of Radiation Oncology*Biology*Physics, 2013

International Journal of Radiation Oncology*Biology*Physics, 2011

Purpose-To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxor... more Purpose-To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials-Patients 70 years old and younger with newly diagnosed, biopsyproven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival.

International Journal of Radiation Oncology*Biology*Physics, 2007

old. Sixteen patients had a GTR, 13 had a STR, 2 patients had a surgical resection but the extent... more old. Sixteen patients had a GTR, 13 had a STR, 2 patients had a surgical resection but the extent of tumor removal was not known and 3 patients did not undergo a surgical resection. Histology was unfavorable in 23, favorable in 4 and unknown in 7 patients. Eleven patients were found to have n-myc amplification, 17 did not, and n-myc status was unknown in 6 patients. Two patients received TBI in preparation for tandem transplantation. The majority of patients had a tandem transplant. The average time from last transplant to the start of local RT was 66.6 days (range 41-136 days). Median radiation dose was 23.2 (range 12-30 Gy, including TBI dose, when applicable). The median dose delivered to patients following a STR was 23.8 Gy. The majority of patients received conventional RT, 6 patients received IMRT. The majority of patients received adjuvant cis-retinoic acid. Results: At the time of analysis 3 patients died of disease, 5 patients were alive with disease, 23 patients were in clinical remission and 3 patients were lost to follow-up. No patients demonstrated failure at the primary tumor site at the time of disease progression. All relapses were distant. Five year Actuarial Overall Survival was 87%. Conclusions: Radiation therapy plays an important role in the local control of neuroblastoma. Our institution has achieved excellent local control in high-risk neuroblastoma patients regardless of resection status. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for both GTR and STR patients in the setting of tandem transplantation and maintenance therapy.

International Journal of Radiation Oncology*Biology*Physics, 2006

The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radioth... more The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapytreated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p ‫؍‬ 0.76) and EFS (11.7 vs. 4.0 months, p ‫؍‬ 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.