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THE ONCOLOGY REPORT (Fall 2006) :: Brain Cancer


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  • 1. BRAINCANCER Brain Cancer Fall 2006 / THE ONCOLOGY REPORT 11 For more meeting reports, visit© 2006 Elsevier Inc. All rights reserved. T he combination of bevaci- zumab (Avastin) and irino- tecan (Camptosar) demon- strated activity against recurrent malignant glioma, resulting in im- proved progression-free survival (PFS) compared with historic con- trols. Furthermore, the combina- tion had acceptable toxicity, includ- ing no CNS hemorrhage, but might increase the risk of thrombosis. “Our future plans are to confirm the safety and efficacy in a random- ized phase II trial of bevacizumab versus bevacizumab and irinotecan in recurrent glioblastoma patients,” announced James J. Vredenburgh, MD, a neuro-oncologist from the Brain Tumor Center at Duke Uni- versity Medical Center in Durham, North Carolina. “We are also going to study bevacizumab in combination with radiation therapy and temo- zolomide (Temodar), followed by 6 months of bevacizumab, irinotecan, and temozolomide in newly diag- nosed patients with glioblastoma.” No approved therapies are avail- ableforrecurrentmalignantgliomas, and the prognosis is poor, reflected in a median survival of < 6 months for grade IV disease and < 15 months for grade III tumors. Irino- tecan has demonstrated some activ- ity against recurrent glioblastoma, with response rates of 0%–15% and Bevacizumab-irinotecan combination shows activity in recurrent glioma Higher-than-expected 6-month PFS and no CNS hemorrhage 6-month PFS of less than 20%, said Dr. Vredenburgh. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has demonstrated synergy with chemotherapy for colorectal, breast, and lung carcinomas. Malignant gliomas have high concentrations of VEGF, and higher concentrations of VEGF have been associated with a poorer prognosis. Antibodies against VEGF have been effective in a xenograft model of malignant glioma. T he study involved 32 patients with histologically confirmed primary malignant glioma and evidence of measurable recur- rent or residual primary CNS neo- plasm on contrast-enhanced MRI. To be eligible for the trial, patients could have no more than three prior recurrences and no evidence of CNS hemorrhage on baseline MRI or CT scan. Major surgery within 28 days or minor surgical procedures within 7 days of enrollment also ruled out participation in the study. Treatment consisted of irino- tecan (125 mg/m2 , 340 mg/m2 for patients on enzyme-inducing anti- convulsants) and bevacizumab (10 mg/kg) every 2 weeks. No patient developed CNS hemorrhage during treatment. Two patients had pulmo- nary emboli, one had deep venous thrombosis, and one had an arte- rial stroke. Two patients developed grade 2 proteinuria, which required withdrawal from the study as stipu- lated in the protocol. Two investigators independently reviewed every MRI scan, measured the enhancing tumor, and reviewed the T2 and FLAIR (fluid-attenuated inversion recovery) sequences. Dr. Vredenburgh reported that 20 of 32 patients had at least a partial re- sponse. The 6-month PFS was 38%, including 30% in patients with grade IV disease and 56% in those with grade III disease. The median PFS was 23 weeks, and the median overall survival was 40 weeks. “The most plausible theory for the efficacy of bevacizumab is the normalization of the tumor vascu- lature, with a marked decrease in the interstitial pressure around the tumor, and increased delivery of the cytotoxic agent to the tumor,” Dr. Vredenburgh concluded. Vredenburgh JJ, Desjardins A, Herndon JE, et al. Bevacizumab, a monoclonal anti- body to vascular endothelial growth factor, and irinotecan for treatment of malignant gliomas. abstract 1506 Dr. Vredenburgh et al have reported the highest response rate ever noted in the literature for patients with recurrent malignant glioma (includ- ing glioblastoma multiforme). The mechanism of this activity is poorly un- derstood, since irinotecan (Camptosar) only produces marginal response in about 5% of patients with recurrent glioblastoma multiforme. Bevacizumab (Avastin) is only now receiving evaluation as a single agent, and it remains unclear whether it is the combination of these two agents or bevacizumab alone. Accordingly, a 12-institution registration trial has just opened; it will evaluate patients with first- or second-relapse glioblastoma multiforme treated with either bevacizumab or bevacizumab plus irinotecan. Should these results be replicated in this larger multi-institutional study, an impor- tant intervention for recurrent glioblastoma multiforme will have been iden- tified, perhaps offering a means of improving the current modest results for patients with newly diagnosed disease when patients are treated with more definitive care. —Henry S. Friedman, MD Comment Brain Cancer Commentary by Henry S. Friedman, MD Modafinil improves neurocognitive function in brain tumor patients Fatigue and depression scores also improved significantly during 12 weeks of treatment T he US Food and Drug Ad- ministration (FDA)-approved medication for various sleep disorders, modafinil (Provigil) sig- nificantly improved neurocognitive function during a 12-week study involving adult patients with brain tumors. In addition to neurocogni- tive abilities, fatigue and depression improved, and clinically meaningful improvement was documented dur- ing weeks 8–12. “Modafinil was very effective at improving neurocognitive abilities, primarily the attention required for INDEX Bevacizumab (Avastin), 11 Chromosome translocation t(1;19), 12 Classification of high-grade gliomas, 13 Clinical trials NCCTG 86-72-51, 12 NCCTG 93-72-02, 12 Irinotecan (Camptosar), 11 Modafinil (Provigil), 11 Neurocognitive function, 11 Prognosis, impact of necrosis on, 13 Risk stratification of gliomas, 14
  • 2. BRAINCANCER 12 THE ONCOLOGY REPORT / Fall 2006 Brain Cancer For more meeting reports, visit© 2006 Elsevier Inc. All rights reserved. This report is the latest observation regarding the ability of pharmaco- logic intervention to improve neurocognitive function in adult patients with brain tumors. Prior studies have addressed the benefits of agents such as donepezil (Aricept) and methylphenidate, and the study follows in that vein. However, modafinil (Provigil) was particularly effective in improving neuro- cognitive abilities as well as fatigue, with acceptable toxicity. Future work should be continued to improve the quality of life in an increasing population of long-term survivors of brain tumors. —Henry S. Friedman, MD Comment T he chromosomal transloca- tion t(1;19)(q10;p10) medi- ates the 1p/19q codeletion and confers a favorable prognosis in patients diagnosed with low-grade oligodendroglioma. “The presence of the trans- location was highly correlated with combined deletion of 1p and 19q,” revealed Robert Jenkins, MD, PhD, professor of labora- tory medicine from Mayo Clinic School of Medicine in Rochester, Minnesota. “Combined 1p/19q deletion as well as t(1;19) trans- location are associated with sig- nificantly prolonged overall and progression-free survival (PFS) in patients with low-grade gliomas. Upon COX modeling, t(1;19) Chromosomal translocation confers favorable prognosis in brain tumors The t(1;19) translocation mediates the 1p/19q codeletion, previously associated with a favorable outcome Prior studies have clearly demonstrated that 1p/19q codeletions confer a favorable prognosis in patients with low-grade oligodendroglioma. This work advances this finding, demonstrating that the 1p/19q codeletion is mediated by the t(1;19) translocation. This is an important observation and may lead to critical studies that demonstrate the biologic underpinning of the relationship between these molecular changes and outcomes. These results could also lead to a change in the therapeutic strategies for patients with and without these molecular abnormalities. —Henry S. Friedman, MD Comment higher cortical functions to perform more efficiently,” said Thomas Ka- leita, PhD, assistant professor of psychiatry from the University of California at Los Angeles. It also was effective at improv- ing fatigue levels, as documented by patient-completed questionnaires. Somewhat surprisingly, the investi- gators found that numerous patients had statistically significant and clin- ically meaningful improvements in mood at 8 and 12 weeks after the initiation of modafinil. The drug was generally well tolerated, with a low incidence of adverse events, he reported. T he study began with a 3- week phase, when patients were started on modafinil at 100 mg/d in the morning for 3 days followed by 200 mg/d in divided doses for 4 days, according to the start-up guidelines of the manufac- turer. The patients were then ran- domized to receive 200 versus 400 mg/d in divided doses. After a 1-week washout period, when they received no medication, patients entered an 8-week open- label treatment extension, when most of them were again started according to the manufacturer’s guidelines: 100 mg/d for 3 days, followed by 200 mg/d for 4 days, and then dose titration up to 600 mg/d either in a single dose or in di- vided doses until their participation in the clinical trial ended. However, about 25% of the patients could not tolerate the daily dose of 200 mg/d but instead had significant improve- ments using 50 to 150 mg/d con- sistently throughout the open label phase of treatment. Dr. Kaleita and his colleagues in the UCLA NeuroOncology Pro- gram enrolled 30 patients, whose mean age was 45.3 years. All had primary malignant or nonmalig- nant cerebral tumors. The patients had moderate to severe fatigue and/or attention or memory im- pairment, as documented by the Clinical Global Impression of Se- verity scale. Exclusion criteria included current treatment with psychostimulants, tricyclic antide- pressants, monoamine oxidase in- hibitors, irinotecan (Camptosar), and experimental chemotherapy. All but two patients had undergone neurosurgical resection, 26 of 30 had received radiotherapy, and 21 had received chemotherapy. Sever- al patients received chemotherapy throughout their participation in the UCLA study. The impact of treatment was assessed by widely used neurocog- nitive tests: Trail Making A and B, Symbol Digit Modalities Test, and Verbal Fluency. “All three of these cognitive measures have been standardized with adults in age ranges up to 90 years old and are timed with a stopwatch. Each of them involves elements of at- tention and concentration in addi- tion to brain-processing speed to complete the task,” indicated Dr. Kaleita. Depression symptoms were as- sessed by the 31-item Hamilton De- pression Scale (HAM-D-31), which includes items addressing fatigue and sleep. Three patient-reported fatigue measures were employed in the study. S ignificant improvements in all cognitive outcome measures occurred at 8 and 12 weeks. The magnitude of improvement ranged from 20% to 33% at week 8 and 20% to 28% at week 12. At baseline, the patients had a mean HAM-D-31 score of 17.8, reflect- ing moderate depression overall as a group. By 8 weeks, scores had im- proved by an average of 7.6 points (43%; P < 0.0001); by 12 weeks, scores were 5.5 points below base- line (31%; P = 0.004). All three fa- tigue outcome measures improved significantly from baseline at 10 translocation, but not the 1p/19q deletion, was independently as- sociated with low-grade glioma survival.” The data also demonstrated that the translocation and codele- tion affected patients’ response to certain types of treatment. Pa- tients who have oligodendroglio- mas with 1p and/or 19q anomalies seem more likely to respond to chemotherapy or radiation therapy and have better overall survival. A previous intergroup study dem- onstrated that patients who have 1p/19q codeletion have better sur- vival than patients who have either the 1p or 19q deletion (Cairncross G et al. Proc Am Soc Clin Oncol 2004;23:107). I nvestigators evaluated the im- pact of the t(1;19) transloca- tion in 134 patients with glioma from two clinical trials conducted by the North Central Cancer Treat- ment Group (NCCTG). NCCTG 86-72-51 was a randomized phase III comparison of 50.4 vs 64.8 Gy of radiation therapy in patients with newly diagnosed low-grade gliomas (Shaw E et al. J Clin On- col 2002;20:2267–2276). NCCTG 93-72-02 was a phase II trial that evaluated 6 cycles of PCV (pro- and 12 weeks. The magnitude of improvement ranged between 35% and 75% at week 10 and between 38% and 83% at week 12. “The improvements in fatigue levels from baseline were dramatic, and they represent the highest per- centages of change among the three outcome goals that were assessed,” Dr. Kaleita commented. No serious adverse events oc- curred during the trial. The most frequent adverse event was head- ache (13 of 30 patients; 43%), consistent with other clinical trials of modafinil. Other adverse events reported by at least 10% of patients included insomnia, dizziness, dry mouth, depressed consciousness, and nausea, all of which resolved after adjustments in dosages and scheduling of modafinil, without any residual effects. KaleitaTA,WellischDK,GrahamCA,etal. Pilot study of modafinil for treatment of neu- robehavioral dysfunction and fatigue in adult patients with brain tumors. abstract 1503
  • 3. BRAINCANCER Brain Cancer Fall 2006 / THE ONCOLOGY REPORT 13 For more meeting reports, visit© 2006 Elsevier Inc. All rights reserved. carbazine [Matulane], lomustine [CEENu], and vincristine) chemo- therapy followed by radiation ther- apy (Buckner JC et al. J Clin Oncol 2003;21:251–255). CEP1/19p12 fusion was informa- tive in 89 of the 134 patients. The prevalence of CEP1/19p12 fusion was 54% in 41 oligodendrogliomas, 46% in 30 mixed oligoastrocyto- mas, and 6% in 18 astrocytomas. CEP1/19p12 fusion was present in 91/% of gliomas with 1p/19q code- letion versus 10% of gliomas with- out the codeletion (P < 0.0001). P atients with the 1p/19q code- letion had a median overall survival of 11.9 months, com- pared with 8.1 months for one or no deletion (P = 0.0041). Evaluation of overall survival by the 1p/19q code- letion and t(1;19) translocation sta- tus demonstrated that the presence of either one was associated with improved survival in patients with gliomas, oligodendrogliomas and mixed oligoastrocytomas combined, and oligodendrogliomas alone. Considering all low-grade gli- oma cases in the study, investiga- tors found that the 1p/19q codele- tion significantly affected overall survival in univariate analysis and the t(1;19) translocation conferred significantly better survival in both univariate and multivariate analy- ses. Separate analyses showed that t(1;19) translocation was signifi- cantly associated with overall sur- vival in combined patients with mixed oligoastrocytomas and oli- godendrogliomas (univariate and multivariate) and in patients with oligodendrogliomas (univariate). Codeletion of 1p and 19q had a significant association with surviv- al among combined patients with mixed oligoastrocytomas and oligo- dendrogliomas (univariate only). Analysis of survival by treat- ment and t(1;19) status in NCCTG 86-72-51 revealed an estimated median survival of 11.6 months in patients who had the translocation Five-year survival rates by t(1;19) translocation status Oligodendroglioma Astrocytoma Mixed oligo/astro Frequencies n 42 20 30 t(1;19) 23 (55%) 1 (5%) 14 (47%) No t(1;19) 19 (45%) 19 (95%) 16 (53%) OS at 5 years t(1;19) 96% 100% 93% No t(1;19) 68% 74% 50% PFS at 5 years t(1;19) 83% 100% 71% No t(1;19) 63% 53% 50% Oligo = oligodendroglioma; Astro = astrocytoma; OS = overall survival; PFS = progression-free survival Spontaneous necrosis influences the accuracy of glioma grading Modification in present WHO criteria might lead to more appropriate treatment I ncorporating spontaneous tu- mor necrosis into the grading of high-grade gliomas could lead to more accurate classification and appropriate treatment of ana- plastic oligoastrocytomas, results of a retrospective review of pathol- ogy data on almost 1,000 gliomas suggest. Analysis of the impact of necrosis on prognosis showed that anaplastic oligoastrocytomas should be stratified on the basis of necrosis into grade III (anaplastic oligoastro- cytoma) and grade IV (glioblastoma multiforme with oligodendroglial features). “High-grade mixed oligoastro- cytomas with spontaneous necro- sis should be classified as WHO (World Health Organization) grade IV neoplasms and designated either mixed oligoastrocytoma, grade IV or, equivalently, glioblastoma mul- tiforme with oligodendroglial fea- tures,” said C. Ryan Miller, MD, PhD, from Washington University in St. Louis. “These results suggest that such tumors should be treated more as grade IV neoplasms than grade III.” The review also showed that pure oligodendrogliomas have prognostically favorable behav- ior. Additionally, 1p/19q status is a powerful prognostic variable in high-grade oligodendroglioma and possibly mixed oligoastrocytoma, Dr. Miller added. T he investigators reviewed data on 988 adults with primary cerebral high- grade gliomas. Pathologic findings were available from resection in 78% of cases and from biopsy in the remaining 22%. The patients were followed for an average of 1.4 years, and 48% of the patients were followed until death. Com- plete data were available for 63% of the cases. Necrosis was present in 55% of the tumors. Molecular/genetic anal- ysis revealed codeletion of 1p/19q in 38% of 578 tumors tested, am- plification of epidermal growth fac- tor receptor (EGFR) in 33% of 237 tumors, and 10q deletion in 62% of 221 tumors. Evaluation of survival accord- ing to WHO tumor classification showed that patients with glio- blastoma multiforme had a median survival of 9.9 months, increasing to 30.4 months for anaplastic as- trocytomas, 42.0 months for ana- plastic oligoastrocytomas, and 86.8 months for anaplastic oligoden- drogliomas. Comparison of tumors with and without necrosis showed that anaplastic oligodendrogliomas with spontaneous necrosis were as- sociated with a median survival of 83.5 months, compared with 135 months for tumors without necro- sis (P = 0.30). Necrosis did have a signifi- cant impact on survival associated with anaplastic oligoastrocytomas. The presence of necrosis was as- sociated with a median survival of 16.9 months, compared with 62.8 months for tumors without necrosis (P < 0.0001). The analysis of molecular and genetic factors associated with dif- ferent tumor subtypes showed that codeletion of 1p/19q occurred tion (P = 0.004). Among patients randomized to receive the lower dose of radiation therapy, patients without the translocation had a me- dian overall survival of 8.1 months, whereas the median survival has yet to be reached in patients with the translocation (P = 0.07). Analysis of a small number of patients from NCCTG 93-72-02 revealed a significant association between t(1;19) translocation and PFS and a trend toward improved overall survival. Codeletion of 1p/19q also demonstrated a non- significant trend toward improved overall and PFS. Jenkins RB, Ballman KV, Giannini C, et al. Diagnostic and prognostic significance of a t(1;19)(q10;p10) in patients with low- grade oligodendroglioma and astrocytoma: NCCTG 94-72-53. abstract 1505 and were treated with the higher dose of radiation therapy versus 5.0 months for patients without the transloca- This abstract clearly demonstrates the valuable information provided by evaluating patients with anaplastic oligodendroglial tumors using molecular analysis and documentation of necrosis. Although histology is obviously the launching point, classification of these malignant glial tumors by quantitation of markers such as 1p and 19q loss and, in this study, necrosis is clearly help- ful in predicting response to current therapy. This analysis will make it easier to find a cohort of patients who may benefit from more rigorous therapy. It should be remembered, however, that as with many other neoplasms, the biologic relevance of any finding, including necrosis or molecular abnormali- ties, can easily change as therapies evolve. It is clear that under the current therapeutic strategies, patients with necrosis will do worse. However, as new interventions are brought into the clinic, these parameters will have to be re-evaluated. —Henry S. Friedman, MD Comment
  • 4. BRAINCANCER 14 THE ONCOLOGY REPORT / Fall 2006 Brain Cancer For more meeting reports, visit© 2006 Elsevier Inc. All rights reserved. in 80% of anaplastic oligoden- drogliomas, accounting for most instances of that genetic trait. EGFR amplification was present in half of the glioblastoma multi- forme specimens and about 10% of the anaplastic astrocytomas and anaplastic oligoastrocytomas. In- stances of 10q deletion were more evenly distributed, including 80% of glioblastoma multiforme, 50% of anaplastic astrocytomas, 20%– 25% of anaplastic oligoastrocyto- mas, and 10%–15% of anaplastic oligodendrogliomas. Codeletion of 1p/19q had a significant adverse effect on sur- vival in patients with anaplastic oligodendrogliomas. Presence of the trait was associated with a median survival of 68.2 months, compared with 135 months with- out the codeletion (P = 0.027). Codeletion was associated with a median survival of 37.5 months in patients with anaplastic oligoas- trocytomas, versus more than 96 months without, although the dif- ference was not statistically sig- nificant (P = 0.23). D r. Miller and colleagues compared the accuracy of the WHO 2000 grading sys- tem and a modified grading system for assessment of mixed oligoastro- cytomas. The modified scheme di- vided mixed oligoastrocytomas into a mixed grade III without necrosis and a mixed grade IV with necrosis. Application of the modified grad- ing system to high-grade oligoden- drogliomas identified patient age and tumor grade as significant pre- dictors of outcome in anaplastic oli- goastrocytomas and age and 1p/19q It is not surprising that the highest 5-year survival is seen in patients younger than age 40 and with a gross total resection. Remarkably, how- ever, the 5-year progression-free survival is actually lower in this group. Nevertheless, these patients can safely and most appropriately be treated with observation alone. Patients who are older than age 40 or who under- went a subtotal resection were randomized to be treated with radiation therapy, with or without chemotherapy. The results are premature, and it is possible that survival can only be positively impacted by the addition of chemotherapy. Whether there is any gain to the initial use of radiotherapy in any setting remains to be seen, although there is compelling evidence that mandates the use of radiotherapy as opposed to initial chemotherapy in this patient population. There are many neuro-oncologists in the United States who withhold radiotherapy until progressive disease is noted, utilizing che- motherapy as a first intervention. —Henry S. Friedman, MD Comment S tratifying low-grade glioma patients by age and extent of surgical resection can identi- fy high- and low-risk patients with respect to overall but not progres- sion-free survival (PFS), investiga- tors in an intergroup study have found. Younger patients with gross total resection had significantly better survival with observation compared with older patients and those with subtotal resection who received radiation therapy with or without chemotherapy. Surpris- ingly, however, PFS did not dif- fer according to the stratification schema. deletion as predictors of outcome for anaplastic oligodendrogliomas. Use of the modified criteria revealed a substantial survival difference be- tween oligoastrocytoma III and IV tumors. Modified oligoastrocytoma III tumors were associated with a median survival of 62.8 months, compared with 16.9 months for modified oligoastrocytoma IV. Miller CR, Dunham CP, Scheithauer BW, et al. Significance of necrosis in grad- ing of anaplastic oligodendroglial tumors: a clinicopathological and genetic study of 988 high-grade gliomas. abstract 1502 Age, resection status fail to define risk in glioma Presumed low-risk patients had better overall but not progression-free survival trial that evaluated high- and low- risk stratification criteria and two treatment strategies for high-risk patients with WHO (World Health Organization) grade II low-grade gliomas, including astrocytoma, oligodendroglioma, and mixed tu- mors. Patients who were younger than age 40 and had undergone gross total resection were assigned to a phase II evaluation of observa- tion. Older patients and those with subtotal resection were randomized to receive radiation therapy (54 Gy in 30 fractions) with or without chemotherapy (procarbazine [Mat- ulane], lomustine [CEENu], and vincristine). The underlying assumption of the study was that high-risk pa- tients would have worse overall survival and PFS compared with low-risk patients. In addition, in- vestigators hypothesized that the addition of chemotherapy to radia- tion therapy would improve 5-year survival in high-risk patients from an estimated 70% to 85%. The study included 111 patients in the low-risk arm and 251 in the two high-risk treatment arms. In comparison to high-risk patients, those in the low-risk group were younger and had smaller tumors; all of them had undergone gross total resection. A s hypothesized, low-risk patients had a significantly better 5-year survival than high-risk patients (93% vs 67%; P < 0.0001). However, 5-year PFS was actually inferior in the low-risk group (48% vs 51%). Univariate analysis showed that larger preop- erative tumor size, astrocytoma his- tology, and greater residual tumor on imaging predicted an increased risk for progressive disease. The addition of chemotherapy to radiation therapy for high-risk patients has yet to improve overall or PFS, Dr. Shaw reported. How- ever, the survival curves began to diverge after 2 years in favor of chemotherapy, and a significant difference might yet emerge with longer follow-up. At the time of the ASCO presenta- tion, overall survival in the radiation therapy group was 87% at 2 years and 62% at 5 years. Overall survival in patients who received chemora- diotherapy was 86% at 2 years and 71% at 5 years. With respect to PFS, the 2-year rates were 73% with ra- diation therapy alone and 72% with chemotherapy. At 5 years, disease- free survival was 42% with radia- tion therapy and 60% with chemo- radiotherapy (P = 0.27). Multivariate analysis showed that older age and astrocytoma histology but not treatment assignment pre- dicted lower survival among high- risk patients. Factors that predicted inferior PFS were astrocytoma his- tology and assignment to radiation therapy alone. The addition of chemotherapy to treatment of high-risk patients substantially increased toxicity, as 67% of patients had grade 3/4 ad- verse events compared with 9% be- ing treated with radiation therapy alone. Dr. Shaw said two-thirds of the grade 3/4 toxicity in the chemo- therapy arm was nonhematologic. Shaw EG, Berkey B, Coons SW, et al. Ini- tial report of Radiation Therapy Oncology Group (RTOG) 9802: prospective studies in adult low-grade glioma. abstract 1500 Progression-free survival in the so-called low-risk patients was actually no different from that in the high-risk patients. “One of the surprises of the analysis has been that the PFS of the so-called low-risk patients was actually no different from the PFS in the high-risk patients,” said Edward G. Shaw, MD, chair of radiation oncology from Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina. “The median PFS for all treatment groups was about 50% at 5 years.” The findings came from a clinical