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We report 2 cases of transitional cell carcinoma, each with a single metastasis to the brain. Both patients underwent craniotomy with resection of the metastatic deposit and adjuvant whole brain radiotherapy. One patient died 4 months later of leptomeningeal carcinomatosis, while the other patient survived 1 year with no evidence of intracranial disease at autopsy despite widespread metastatic involvement of other organs.

ObjectivesGuidelines for the conduct of clinical trials emphasize the importance of keeping the interim results from the main endpoints confidential, in order to maintain the integrity of the trial and to safeguard patients’ interests. However, is this essential in every situation?Materials and methodsWe review the evidence for these guidelines and consider recent randomised trials that have released interim results, to assess their impact on the success of the trial. However, because the strength of opinion to keep interim results confidential is so strong, there are limited examples of such trials.ResultsIn the QUARTZ trial (which is assessing the value of whole brain radiotherapy in patients with brain metastases from non-small cell lung cancer) the decision to release interim results was taken in response to threatened closure due to poor accrual, whereas in the GRIT trial (which compared two obstetric strategies for the delivery of growth retarded pre-term fetuses) the regular release of interim results was pre-planned. Nevertheless there are a number of common factors between these two trials. In particular, the trial treatments were already in wide use, with no reliable randomised evidence on which treatment should be used for which patients, and there was diverse clinical opinion, which meant that accrual was likely to be challenging. In a situation where a quarter to a third of trials do not accrue their required number of patients, the QUARTZ trial continues to accrue patients, and the GRIT trial successfully accrued its target of nearly 600 babies.ConclusionsThis article therefore argues that there is a need to re-consider whether it is always essential to keep the interim results of randomized clinical trials confidential, and suggests some criteria that may help groups planning or running challenging trials decide whether releasing interim results would be a useful strategy.

TPS2103 Background: WBRT is a standard therapy for metastatic breast cancer (MBC) patients with brain metastases (BM). Despite WBRT, disease progression in the brain is common, and survival is poor...

Background Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM. Methods A total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher’s exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire. Results The average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable. Conclusions Adding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated.

BACKGROUND Optimal treatment strategy for newly diagnosed primary PCNSL remains controversial. The high risk of radio-induced late-delayed neurotoxicity in patients who achieve long-term disease control constrains the use of classical consolidation WBRT. So as to reduce side cognitive effects, Morris et al, reported a phase II study, to assess the efficacy and toxicity of consolidation reduced-dose (23.4Gy) WBRT (rdWBRT) for patients with complete response after high dose methotrexate based chemotherapy. The study reported a 2-year PFS rate for these patients of 77%, with no evidence of significant cognitive decline during the follow-up (FU) period. The aim of this retrospective study was to report toxicity and outcomes of rdWBRT, in patients < 60 years old with complete response (CR) after HD-MTX based chemotherapy, in real life setting, without selection bias. MATERIAL AND METHODS Patients were selected from the French LOC network database, a nationwide database centralizing since 2011 information from 28 different centers in France, representing the main centers involved in PCNSL management. Patients were retrospectively selected according to the following criteria: 1) Pathological diagnosis of diffuse large B cell PCNSL; 2) age>18 and 1.5 g/m2); 5) CR according to the IPCG criteria after first-line induction treatment. Patients should have received a rdWBRT (23.4Gy in 13 fractions of 1.8Gy). RESULTS Twenty seven patients, were included. The median FU from initial diagnosis was 28.5 months [9.6–50.7]. Median age was 50.2 years [25–60]. Median Karnofsky Performans Status (KPS) was 90% [40–100%]. Seventeen patients had a multi focal disease at diagnosis (meningeal involvement n=6, in ophthalmic involvement n=4). PFS rates were 85% IC95[76–100 %], 65% IC95 [45–85%] and 65% IC95 [45–85%] at 1, 2, and 3 years respectively. The OS rates were 100%, 90,5% IC95 [77–100%] and 85%IC95 [69–100%]. 8 patients relapsed, with a median time from radiotherapy to recurrence of 6.5months [2.4–17]. All recurrences were outside the initially involved site(s), and 62.5% of tumors recurred as multifocal disease. All patients received salvage treatment, including intensive chemotherapy with autologous stem cell transplantation in 4 cases. No acute grade III-IV toxicity related to rdWBRT was reported. Neuropsychological follow up was available for 14 patients with no cognitive impairment at last follow up. CONCLUSION This is the largest retrospective study evaluating outcomes of rdWBRT for PCNSL young patients with CR after HD-MTX chemotherapy. Real life setting data from this study are quite reassuring, and rdWBRT could be considered as an efficient and safe consolidation strategy in this population. We need a longer FU to confirm the absence of cognitive deterioration.

BACKGROUND: The purpose of this study is to evaluate the overall survival in patients diagnosed with primary cerebral lymphoma (PCNSL) treated with radiotherapy associated with Temozolomide (TMZ) after treatment with high dose methotrexate (HD-MTX). MATERIAL AND METHODS: Patients with an histological diagnosis of PCNSL, receiving HD-MTX, were enrolled to receive Temozolomide concomitant to radiotherapy. The whole brain up to C2 leptomeninges was irradiated by 30 Gy in 15 daily fractions, while the radiation dose to initial or residual disease, if present, was modulated according to the response to HD-MTX (Complete response = 6 Gy, partial response = 10 Gy, progression disease = 16 Gy). Concomitant Temozolomide was administered at a safety dose level of 75 mg/mq according to our previous escalation study. RESULTS: From March 2004 to December 2017 were enrolled 33 patients: 18 males and 15 females. The median age was 64.5 yrs (range 50–76). Twenty two patients received two cycles of HD-MTX, 9 received only one cycle, because of hematological toxicity, and 2 patients did not received any cycle because of poor performance status. Nine patients were subjected to macroscopic surgical excision while the remaining patients were only subjected to biopsy. Twenty-five patients were subjected to radio-chemotherapy with TMZ. The median follow up was 80 months (range 3–169), 9 out of 33 patients (27%) are alive (7 without disease and 2 with stable disease), 22 patients died because of disease and two patients because of other causes. The median survival (OS) of the whole group was 23.1 months with at 1 yrs OS of 64% and at 3 yrs OS of 43%. The concomitant use of TMZ showed a significant impact on OS (P = 0.004). CONCLUSION: This prospective study demonstrated that the use of TMZ at a dose of 75 mg/mq associated with radiotherapy shows better results in terms of OS than radiotherapy alone.

To analyze the outcome of patients with brain oligometastases treated by radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) after whole-brain radiotherapy (WBRT).Overall survival (OS) and local control (LC) were evaluated in patients (patients) with 1-2 brain metastases.Forty-seven patients were selected. They were submitted to WBRT (median dose=3,750 cGy) followed by SRS (17 patients; median dose=1,500 cGy) or FSRT (30 patients; median dose=2,000 cGy). Median follow-up was 102 months (range=17-151); the median survival was 22 months for the SRS group and 16 months for the FSRT group. One-year and 5-year survival was 56% and 16%, respectively, in SRT and 62.1% and 3%, respectively, in FSRT. Neither treatment proved to significantly impact OS (p=0.4). The 1-year LC rates were 80% and 61.1% in the two groups, respectively (p=0.15).SRS or FSRT after WBRT could offer the same outcomes in patients with brain oligometasteses. Further investigation is warranted to confirm these data and define the optimal stereotactic modality.

Background Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. Methods Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. Results The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions