Is oligoprogression a potentially curable disease in epidermal growth factor receptor mutant lung adenocarcinoma?

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate with a positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an EGFR mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of EGFR mutant patients.

Validation of the new Graded Prognostic Assessment scale for brain metastases: a multicenter prospective study.

BACKGROUND: Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. METHODS: A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months. RESULTS: During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. CONCLUSIONS: Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

Pre-operative chemoradiotherapy with UFT and Leucovorin in patients with advanced rectal cancer: a phase II study.

PURPOSE: The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer. MATERIALS/METHODS: Eligibility included biopsy proven rectal adenocarcinoma; T3-T4 N0-N2; performance status < 2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m(2)/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4-6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1-28, every 5 weeks. RESULTS: Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand-foot syndrome 2%. The 3-year disease-free survival was 71%. CONCLUSIONS: Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.

Thallium-201SPECT assessment in the detection of recurrences of treated gliomas and ependymomas.

INTRODUCTION: The aim of this study was to establish the value of thalium-(201) single-photon emission computed tomography ((201)Tl-SPECT) in the detection of recurrences in the follow-up of patients with treated primary neuroepithelial tumours. MATERIAL AND METHODS: Sixty-three (201)Tl-SPECT were performed in 36 patients with glioma (12 males, mean age of 46 +/- 13 years). All patients underwent surgery and adjuvant radiotherapy (and some of them received chemotherapy). All patients were submitted to morphological neuroimaging techniques as well (and (201) Tl-SPECT). Mean follow-up was 18.3 +/- 14.6 months. Gold standard was based on clinical follow-up, therapeutical decisions (at least 4 months after (201)Tl-SPECT) and imaging features. RESULTS: Sensitivity and specificity of (201)Tl-SPECT to detect glioma recurrences were 90% and 100% respectively and 93% accuracy. Sensitivity and specificity for high grade tumours, were 100% respectively. Due to 4 false negatives, sensitivity and specificity for low grade gliomas were 78% and 100%. In the positive (201)Tl-SPECT group of patients overall survival was 13.64% at the end of the study. The negative (201)Tl-SPECT group had 84.62% overall survival at the end of the study (p = 0.0003). CONCLUSIONS. (201)Tl-SPECT is a valuable and noninvasive diagnostic procedure to detect recurrence or progression disease for treated gliomas and ependymomas. (201)Tl-SPECT has a good correlation with short term prognosis with excellent diagnostic accuracy.