Incidence of hippocampal metastases in non-small-cell lung cancer.

OBJECTIVES: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) develop brain metastases in 25-50% of cases during the course of their disease. Data on the incidence of metastases occurring in the hippocampus/perihippocampal zones are limited. This is important when considering hippocampal-sparing brain radiation (HS-BR), a method that could potentially reduce the neurocognitive impact of such treatment. The aim of this study was to assess the incidence of hippocampal/perihippocampal metastases in a cohort of patients with advanced NSCLC treated at our institution. METHODS: This retrospective cohort study included NSCLC patients discussed at our institutional lung cancer multidisciplinary meeting between 2000 and 2016. MRI and contrast-enhanced CT (ceCT) brain images were reviewed to assess the incidence of hippocampal/perihippocampal metastases including metastases within the hippocampal subgranular zone and a 5 mm margin (hippocampal avoidance region) defined as per the RTOG 0933 study. RESULTS: Of 2146 patients reviewed, 357 (16.6%) had brain metastases. A total of 335 patients had available MRI/ceCT brain images for review. Thirty (9%) patients had brain metastases in the hippocampal avoidance region, 8 (2.4%) with hippocampal metastases and 22 (6.6%) with perihippocampal metastases. Univariate analyses did not show an association between developing metastases in the hippocampal avoidance region and age (P = 0.75), gender (P = 0.91) and tumour type (P = 0.298). CONCLUSION: The incidence of metastases in the hippocampal avoidance region in our large cohort of patients was 9%. With low rates of metastases in this region, HS-BR can be considered a feasible option in the management of patients with advanced NSCLC.

Concurrent chemoradiation with cisplatin and vinorelbine followed by consolidation with oral vinorelbine in locally advanced non-small cell lung cancer (NSCLC): the phase II CONCAVE study.

AIM: Despite recent advances, outcomes for patients with stage III non-small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the combination of ciplatin/vinorelbine and concurrent thoracic radiotherapy followed by consolidation oral vinorelbine in this phase II study. METHODS: Eligible patients with unresectable stage III NSCLC received cisplatin intravenous (IV) 40 mg/m2 and vinorelbine IV 20 mg/m2 on days 1, 8, 22 and 29 concurrent with thoracic radiotherapy of 60 Gy in 30 fractions. Four to eight weeks later, oral vinorelbine 60 mg/m2 day 1 and 8 every 3 weeks was given for 3 cycles. The primary end point was overall response rate (ORR). Secondary end points were safety, quality of life, progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven eligible patients were enrolled from December 2007 to June 2010 before the trial was prematurely closed due to toxicity concerns. The median age was 63 years (range, 42-71), 56% were male, 52% ECOG 0 and 52% stage IIIa. The ORR was 81% (including 37% complete response rate) and disease control rate of 93%. The median PFS was 11 months and median OS was 26 months. Consolidation vinorelbine was associated with significant grade 3/4 toxicity (68%) including grade 3-5 febrile neutropenia (27%) and respiratory infections (36%) including two deaths in the consolidation phase (9%). CONCLUSIONS: Consolidation oral vinorelbine after CRT was associated with significant toxicity. Overall, this regimen achieved a high ORR and survival results comparable to other CRT protocols but the significant toxicity precludes further evaluation of this approach.

Outcomes treating stage III non-small cell lung carcinoma with curative-intent radiotherapy and concurrent carboplatin-paclitaxel chemotherapy.

BACKGROUND AND AIM: Thoracic radiotherapy administered concurrently with chemotherapy is the standard of care for patients with inoperable stage III non-small cell lung cancer, but the optimal chemotherapy regimen is not clearly established. The objective of this study was to assess outcomes in a large cohort of patients treated with curative-intent using carboplatin and paclitaxel. METHODS: Consecutive patients undergoing curative-intent radiotherapy to 60-66 Gy in 30-33 daily fractions with concurrent weekly carboplatin (AUC = 2) and paclitaxel (45 mg/m(2) /week) between March 2004 and May 2012 were identified from a prospective database and reviewed individually. A minimum follow-up of 3 months was required unless death occurred sooner. Response to treatment was defined according to established guidelines on re-staging computed tomography scan at 3 months. Toxicities were assessed using a standardised scoring system. RESULTS: One hundred and seven patients were analysed. The median follow-up was 43.5 months. Three months after treatment, a complete or partial response was observed in 72 patients (68%), and nine patients (8%) had already died. The overall locoregional failure rate was 47%, and failure eventually occurred at any site in 75 patients (70%). Median progression-free survival, and median survival were 15 and 22 months, respectively. Grade 3-4 neutropaenia, thrombocytopaenia, nephrotoxicity, oesophagitis and pneumonitis were observed in 15%, 1%, 3%, 11% and 9% of patients during treatment, respectively. There was one episode of fatal radiation pneumonitis. CONCLUSION: Treatment with thoracic radiotherapy and concurrent carboplatin and paclitaxel chemotherapy is feasible. Survival and toxicity outcomes compare favorably to those reported using cisplatin-based regimens.