scholarly journals Measuring Bias in Uncontrolled Brain Tumor Trials – to Randomize or Not to Randomize?

1997 ◽  
Vol 24 (04) ◽  
pp. 307-312 ◽  
Author(s):  
William D. Irish ◽  
David R. Macdonald ◽  
J. Gregory Cairncross
Keyword(s):  
Malignant Glioma ◽  
Stereotactic Radiosurgery ◽  
Selection Bias ◽  
Median Survival ◽  
Patient Selection ◽  
Selection Process ◽  
Phase Iii ◽  
Entire Group ◽  
Survival Times ◽  
The Impact

ABSTRACT:Purpose:To help investigators decide if new therapies for glioma warrant definitive evaluation in randomized studies we have been developing a method for assessing the degree to which patient selection may have enhanced the results of uncontrolled treatment trials. In this study, we analyzed the impact of case selection on the survival of patients with malignant glioma receiving adjuvant stereotactic radiosurgery, a promising therapy reserved for those with small tumors and good performance status.Methods:Following published eligibility criteria we simulated the patient selection process for stereotactic radiosurgery given as a boost at the conclusion of conventional radiotherapy. Eligible patients were culled from a pre-existing clinical/imaging database of 101 consecutive conventionally-treated patients with biopsy-proven malignant glioma and known survival times. Median durations of survival and 2- and 3-year survival rates were determined for those judged eligible or ineligible for stereotactic radiosurgery.Results:Twenty-seven percent of patients were deemed eligible for stereotactic radiosurgery, eligible patients had more favorable prognostic factors and significantly longer median survival than ineligible patients (23.4 vs. 8.6 months; 2-year rate, 48% vs. 15%; 3-year rate, 30% vs. 7%); eligible patients also had a longer median survival than the entire group of unselected patients (23.4 vs. 11.4 months). Radiosurgery-eligible, conventionally-treated patients with glioblastoma multiforme and a group of radiosurgery-treated patients at a special referral center had similar median survival times (16.4 vs. 19.7 months).Conclusion:We provide additional evidence for selection bias in uncontrolled trials of stereotactic radiosurgery and by simulating the selection process accurately have detected a larger bias effect than noted previously. Judging from experience with interstitial radiation and intraarterial chemotherapy where substantial selection bias also occurred and randomized controlled trials proved disappointing, we conclude that a phase III study of stereotactic radiosurgery for malignant glioma is unlikely to yield a positive result and may not be necessary.

scholarly journals RADT-23. IMPACT OF REIRRADIATION UTILIZING STEREOTACTIC RADIOSURGERY ON RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
High Performance ◽  
Performance Status ◽  
Treatment Options ◽  
Methylation Status ◽  
Initial Therapy ◽  
Recurrent Glioblastoma ◽  
Control Group ◽  
The Impact

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P < 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P< 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.

scholarly journals Survival Among Patients With Pancreatic Cancer and Long-Standing or Recent-Onset Diabetes Mellitus

2015 ◽  
Vol 33 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Chen Yuan ◽  
Douglas A. Rubinson ◽  
Zhi Rong Qian ◽  
Chen Wu ◽  
Peter Kraft ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Case Series ◽  
Health Study ◽  
Survival Times ◽  
Recent Onset ◽  
Onset Diabetes ◽  
Diabetes Status ◽  
The Impact

Purpose Long-standing diabetes is a risk factor for pancreatic cancer, and recent-onset diabetes in the several years before diagnosis is a consequence of subclinical pancreatic malignancy. However, the impact of diabetes on survival is largely unknown. Patients and Methods We analyzed survival by diabetes status among 1,006 patients diagnosed from 1986 to 2010 from two prospective cohort studies: the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). We validated our results among 386 patients diagnosed from 2004 to 2013 from a clinic-based case series at Dana-Farber Cancer Institute (DFCI). We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and cancer stage. Results In NHS and HPFS, HR for death was 1.40 (95% CI, 1.15 to 1.69) for patients with long-term diabetes (> 4 years) compared with those without diabetes (P < .001), with median survival times of 3 months for long-term diabetics and 5 months for nondiabetics. Adjustment for a propensity score to reduce confounding by comorbidities did not change the results. Among DFCI patient cases, HR for death was 1.53 (95% CI, 1.07 to 2.20) for those with long-term diabetes compared with those without diabetes (P = .02), with median survival times of 9 months for long-term diabetics and 13 months for nondiabetics. Compared with nondiabetics, survival times were shorter for long-term diabetics who used oral hypoglycemics or insulin. We observed no statistically significant association of recent-onset diabetes (< 4 years) with survival. Conclusion Long-standing diabetes was associated with statistically significantly decreased survival among patients with pancreatic cancer enrolled onto three longitudinal studies.

scholarly journals 55. A RANDOMIZED, MULTICENTER PHASE III TRIAL OF SURGERY PLUS STEREOTACTIC RADIOSURGERY (SRS) COMPARED WITH SURGERY PLUS PERMANENTLY IMPLANTED COLLAGEN TILE BRACHYTHERAPY (CTBT) FOR RESECTABLE METASTATIC BRAIN TUMORS-PROTOCOL IN PROGRESS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
Jeffrey Weinberg ◽  
Mary Frances McAleer ◽  
Hussein Tawbi ◽  
Frederick Lang
Keyword(s):  
Brain Tumors ◽  
Stereotactic Radiosurgery ◽  
Word Association ◽  
Verbal Learning ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Karnofsky Performance Scale ◽  
Metastatic Brain Tumors ◽  
Recurrence Rates ◽  
The Impact

Abstract BACKGROUND Resection (R) followed by single or multi-fraction stereotactic radiosurgery (SRS) lowers resection bed recurrence compared to R alone. Nevertheless for larger brain metastasis (&gt;2.5 cm) 12-month recurrence rates after R+SRS can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy (CTBT) device (GammaTile, GT Medical Technologies, Tempe AZ) utilizing Cs-131 was developed, hypothesizing that immediate adjuvant radiotherapy (RT) and/or RT dose intensification could improve outcomes. The device received FDA clearance for this indication, based on a single-arm pre-commercial study and in early commercial use due to the excellent safety and local control of R+CTBT. It is hypothesized that R+CTBT will increase the time to post-resection-recurrence, while prolonging survival and reducing the impact on functional and neurocognitive status compared to R+SRS. STUDY DESIGN Multicenter, randomized, comparison trial. Patients with resectable, previously untreated “index” brain metastases measuring &gt;2.5–5 cm and 0–3 other tumors will be preoperatively randomized 1:1 to undergo either R+ SRS or R+CTBT to the index lesion; unresected tumors in both groups will receive SRS. Planned sample size is 160 from ~5 sites; accrual to start in Q3-2020. Primary endpoint is surgical bed-recurrence free survival. Secondary endpoints include overall survival, quality of life (Functional Assessment of Cancer Therapy-Brain, Linear Analog Self-Assessment), neurocognition (Hopkins Verbal Learning Test, Trail Making Tests, Mini-Mental Status Exam, Controlled Oral Word Association), functional decline (Karnofsky Performance Scale, Barthel-ADL), and adverse events. Follow-up will be at 1,3,6,9, and 12 months, then q 6 months through 5 years. CONCLUSIONS This will be the first randomized trial comparing R+SRS versus R+CTBT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures will be captured to elucidate the potential risks and benefits of these two differing approaches for patients with metastatic brain tumors.

A novel intermediate endpoint for predicting overall survival in men with metastatic castration-recurrent prostate cancer (CRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5113-5113 ◽  
Author(s):  
S. Halabi ◽  
S. Ou ◽  
N. J. Vogelzang ◽  
H. Scher ◽  
E. J. Small
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Clinical Benefit ◽  
Opioid Analgesic ◽  
Performance Status ◽  
Phase Iii ◽  
Training Dataset ◽  
Survival Times ◽  
Androgen Ablation ◽  
Three Components

5113 Background: In this proposed study, we developed and validated a novel composite clinical benefit endpoint constructed from symptoms that have intrinsic clinical importance in 800 men with CRPC who were treated with front-line chemotherapy. Methods: Data from nine multimember trials (five phase II and four randomized phase III studies) conducted by the Cancer and Leukemia Group B (CALGB) from 1992–2004 were combined. Eligible patients had progressive adenocarcinoma of the prostate during androgen ablation (despite castrate testosterone levels), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic functions. The tripartite composite clinical benefit endpoint (TCCBE) had three components: one based on disease progression (whether it be PSA, bone, or soft tissue progression), and the second based on weight loss (defined as at least 10% decline from baseline) or on performance status (PS) decline (by at least one level) to capture clinical deterioration. The third component was based on pain control and opioid analgesic use (no or yes). For a person to fall in the TCCBE “yes” category, at least two of the three components had to be recorded as no. For instance, if a patient at 3 months had no progression, no change in weight and did not use opioid analgesic, then he will be classified in the “yes” group and for the purpose of this analysis was considered as someone who achieved “clinical benefit”. The sample was randomly split into 526 (67%) and 274 (33%) men in the training and testing datasets, respectively. Results: From the training dataset, the median survival times in men who had and did not have clinical benefit were 20.9 months (95% confidence interval (CI) = 18.5–22.8) and 11.1 months (95% = 8.79–12.6, p- value<0.001). In the testing dataset, the median survival times in men with and without clinical benefit were 21.7 months (95% CI= 19.1–26.1) and 8.8 months (95% CI= 7.8–11.6) and in men. The hazard ratio (HR) for men with a clinical benefit compared to men without was 0.52 (95% CI= 0.43–0.62, P<0.001). Conclusions: The TCCBE is a statistically significant intermediate endpoint for predicting overall survival. Prospective validation of this endpoint is needed. No significant financial relationships to disclose.

Serum cathepsin B (CB) levels are prognostic in chemotherapy-naive patients (pts) with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18036-18036
Author(s):  
J. W. Singer ◽  
F. B. Oldham ◽  
B. Bandstra ◽  
L. Sandalic ◽  
J. Bianco ◽  
...  
Keyword(s):  
Median Survival ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Phase Iii ◽  
Serum Samples ◽  
Protein Levels ◽  
Lysosomal Cysteine Protease ◽  
Phase Iii Trials ◽  
And Performance ◽  
The Impact

18036 Background: CB is an estrogen-influenced lysosomal cysteine protease produced by tumor cells and tumor-associated macrophages; tumor tissue CB protein levels and proteolytic activity are prognostic in NSCLC (Anticancer Res. 2004; 24:4147–61). The prognostic value of serum CB has not previously been evaluated in NSCLC. Here we evaluate the impact of pretreatment CB levels on survival in pts from 2 phase III trials in advanced NSCLC, STELLAR 3 and 4. These trials compared paclitaxel poliglumex (PPX) against commonly used regimens. As the intratumoral metabolic pathway of PPX is characterized by the CB-mediated release of paclitaxel (P) from a polymeric backbone (Ca Chemother Pharm. 2006. Epub ahead of print), correlation of CB levels with PPX efficacy was assessed as well. Methods: Pretreatment serum samples from 450 chemo-naive pts with advanced NSCLC and PS 2 enrolled in STELLAR 3 (P + carboplatin (C) v. PPX + C) (N=315) and STELLAR 4 (vinorelbine or gemcitabine v. PPX) (N=135) were assayed for CB by ELISA (ICON Labs). Values were assessed by quartiles and there was a clear breakpoint at the median. Pts were categorized as high or low CB based on values above or below the median (64 ng/ml). The effect of CB levels on survival was evaluated by log rank for pooled pts from the studies. Results: As detailed in the table , median survival for non-PPX-treated pts was worse if CB was high; in contrast, median survival for PPX-treated pts did not differ by CB level. Pts with high CB receiving PPX showed a trend towards better survival compared to those receiving control regimens. Conclusions: The data suggest that serum CB may be prognostic biomarker for NSCLC. Retrospective analysis suggests a trend towards improved survival in patients with high CB receiving PPX; prospective studies are required to confirm this observation. [Table: see text] No significant financial relationships to disclose.

Sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer: Experience of a Brazilian oncological center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12105-e12105
Author(s):  
Daniel D’Almeida Preto ◽  
André Octavio Nicolau Sanches ◽  
Alison Wagner Azevedo Barroso ◽  
Alessandra Caroline Moretto Carbinatto ◽  
Ana Lima Veneziani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Cancer Center ◽  
Survival Times ◽  
Number Of Patients ◽  
The Impact

e12105 Background: The best sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer is still unknown. The aims of this study were to assess the impact of the sequence order in the pathological complete response (pCR) rate, and in the disease free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed 235 HER2-negative breast cancer women treated with neoadjuvant chemotherapy from 2003 to 2011 at our cancer center. The patients were pooled in two groups: anthracycline-based followed by taxanes (AC-T) and the reverse sequence (T-AC). The chi-square test was performed to verify the homogeneity between the groups and to compare pCR rate among the treatment groups. Cumulative survival probabilities were calculated using the Kaplan-Meier method. Differences between survivals were tested using the log-rank test. Results: The AC-T (n = 161) and T-AC (n = 74) groups were balanced for age, staging, receptor profile and histologic grade. The follow-up was at least five years for each patient. The median age was 50.1 years. Most patients (97%) had stage III tumors and 72 (30%) had triple negative disease. pCR rate was higher in triple negative compared with luminal cases (16.3 vs. 7.3%; p = 0.049). Treatment sequence did not influence the occurrence of pCR (10.5 vs. 8.5%; p = 0.8) or median survival times (DFS: 87.9 vs. 64.1, p = 0.85; OS: 91.1 vs. 71.6 months, p = 0.15), in the AC-T and T-AC groups, respectively. Conclusions: The sequence of neoadjuvant taxane-anthracycline-based chemotherapy regimen in daily practice did not show difference in the evaluated clinical outcomes. The retrospective design and the low number of patients may limit the power of the study to detect statistically significant differences. Phase III trials should be stimulated in this context. [Table: see text]

scholarly journals Bias, benefit, or both: evaluating new glioma therapies

1998 ◽  
Vol 4 (6) ◽  
pp. E11 ◽  
Author(s):  
James R. Perry
Keyword(s):  
Malignant Glioma ◽  
Selection Bias ◽  
Phase Ii ◽  
Clinical Trial Design ◽  
Treatment Resistance ◽  
Phase Iii ◽  
Outcome Analysis ◽  
Tumor Control ◽  
Phase Ii Trials ◽  
Therapeutic Trials

Despite the development of many new promising therapies for malignant glioma, virtually all randomized controlled trials testing them have proven negative. These disappointing results are largely due to complex mechanisms of treatment resistance, but increasingly there is evidence that experimental bias rather than benefit accounts for both the promising early phase I/II trial results and later phase III failures. This paper highlights the aspects of clinical trial design and outcome analysis that specifically affect interpretation of results from therapeutic trials for malignant glioma. Phase II trials of both tumor response and tumor control are subject to selection bias; the early promising results seen with interstitial brachytherapy and intraarterial chemotherapy and yet negative phase III results are examples of this. Methods for detecting selection bias include modeling techniques in which databases of patients with known outcomes are used to emulate phase III outcomes. Modeling may assist in the determination of whether a given phase II result appears to exceed that expected by selection bias alone. Such an experiment on paper is quite unlikely to replace a well-designed randomized trial; however, in this time of increasing numbers of novel therapies but shrinking resources, these techniques should find utility in selecting those therapies most suitable for testing in cooperative group randomized trials.

Phase III study comparing cisplatin/vinorelbine plus cetuximab versus cisplatin/vinorelbine as first-line treatment for patients with epidermal growth factor (EGFR)-expressing advanced non-small cell lung cancer (NSCLC) (FLEX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7109-7109 ◽  
Author(s):  
J. Von Pawel ◽  
K. Park ◽  
J. R. Pereira ◽  
A. Szczesna ◽  
C. Yu ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Advanced Nsclc ◽  
Safety Information ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
Survival Times ◽  
First Line

7109 Background: Cisplatin plus vinorelbine is a commonly used regimen for first-line therapy of advanced NSCLC, achieving response rates of 20–30% and median survival times of 6 to 11 months (mths). An earlier phase II trial investigated cetuximab in combination with cisplatin and vinorelbine in this setting and found improved response rates in the cetuximab arm, warranting this larger phase III trial. Methods: Patients (pts) with EGFR-expressing advanced NSCLC (stage IIIB with documented malignant pleural effusion and stage IV) were randomized 1:1 either to Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2 weekly, cisplatin 80 mg/m2 on day 1, vinorelbine 30 mg/m2 on day 1 and 8) or to Group B (cisplatin and vinorelbine as before) for a maximum of 6 three-weekly cycles. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, tumor response, disease control, safety, and quality of life. Enrollment of 1,100 pts was planned to show an increase of median survival time of 25% with 90% power. The Data Safety Monitoring Board (DSMB) performed an independent preplanned safety analysis from the first 370 pts. Patients were followed for a minimum of 6 weeks (2 cycles). Results: Since November 2004, 1,037 pts have been randomized, 689 are under treatment, and 348 pts have discontinued the study. Demographics of the first 370 pts reflected known advanced NSCLC characteristics: 91% stage IV, median age 60 yrs (31–79), 38% female, 80% ECOG PS 0/1, 52% adenocarcinoma, 30% squamous cell carcinoma; 29% never-smokers, 17% Asian. The ten most frequent adverse events were: nausea, neutropenia, vomiting, anorexia, fatigue, constipation, anemia, febrile neutropenia, rash, and diarrhoea. Conclusions: The trial continued after review of all relevant baseline and safety information from the first 370 pts. Recruitment is ongoing. [Table: see text]

Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials

2006 ◽  
Vol 24 (24) ◽  
pp. 3871-3879 ◽  
Author(s):  
Jan C. Buckner ◽  
Karla V. Ballman ◽  
John C. Michalak ◽  
Gary V. Burton ◽  
Terrence L. Cascino ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Survival Rates ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Survival Times ◽  
North Central ◽  
Newly Diagnosed Glioblastoma ◽  
Improvement In Survival

Purpose In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). Patients and Methods After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). Results Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). Conclusion Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.

Phase III Trial of Chemotherapy Plus Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402

2006 ◽  
Vol 24 (18) ◽  
pp. 2707-2714 ◽  
Author(s):  
Gregory Cairncross ◽  
Brian Berkey ◽  
Edward Shaw ◽  
Robert Jenkins ◽  
Bernd Scheithauer ◽  
...  
Keyword(s):  
Median Survival ◽  
Radiation Therapy Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Anaplastic Oligodendroglioma ◽  
Allelic Loss ◽  
Survival Times ◽  
Free Survival ◽  
The Status ◽  
Grade 3

Purpose Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss. Patients and Methods Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization. Results Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P ≤ .001); longer progression-free survival was most apparent in this subset. Conclusion For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.

Sign in / Sign up

Export Citation Format

Share Document