Labyrinthine enhancement on 3D black blood MR images of the brain as an imaging biomarker for cisplatin ototoxicity in (lung) cancer patients.

PURPOSE: Cancer patients treated with platinum-based chemotherapy can present with ototoxicity symptoms. The purpose of this work is to report the imaging features related to cisplatin ototoxicity. METHODS: Between December 2015 and March 2019, a cohort of 96 consecutive patients with lung cancer was selected. Only patients who received cisplatin chemotherapy and underwent an imaging protocol consisting of a Gd-enhanced 3D-BB and 3D-T1W sequence, as well as T2W sequence to exclude metastases, were included. Labyrinthine enhancement was assessed, and all findings regarding the auditory and vestibular function were retrieved from the clinical files. RESULTS: Twenty-one patients met the inclusion criteria. The Gd-enhanced 3D-BB images were used to divide them into the labyrinth enhancement group (LEG) and the labyrinth non-enhancement group (LNEG). None of these patients demonstrated enhancing regions on the 3D-T1W images. The labyrinthine fluid remained high on the T2 images in all patients, excluding metastases. The LEG consisted of 6 patients. The cochlea and semicircular canals were the most frequently affected regions. All the LEG patients that presented with hearing loss (4/6) had cochlear enhancement. Patients with normal hearing had no cochlear enhancement. Five patients (5/6) showed vestibular enhancement. Four of these patients had vestibular symptoms. CONCLUSION: Labyrinthine enhancement as an imaging feature related to cisplatin ototoxicity is unreported. This study demonstrates a correlation between hearing loss and cochlear enhancement and also between vestibular impairment and vestibular/semicircular enhancement on 3D-BB images, which remained invisible on the 3D-T1W images. The labyrinthine enhancement on 3D-BB images in the presence of normal signal intensity of the intralabyrinthine fluid can be used as an imaging biomarker for cisplatin toxicity in daily clinical practice and should not be mistaken for intralabyrinthine metastases.

Does nivolumab for progressed metastatic lung cancer fulfill its promises? An efficacy and safety analysis in 20 general hospitals.

OBJECTIVES: In patients with refractory or recurrent non-small-cell lung cancer (NSCLC) after first line chemotherapy, phase III trials showed superiority of nivolumab, an IgG4 programmed death-1 immune-checkpoint-inhibitor antibody, over docetaxel. We evaluated case mix, effectiveness and safety of nivolumab upon implementation in general practice. MATERIALS AND METHODS: In 20 general hospitals, all consecutive NSCLC patients treated with nivolumab within the medical need program (inclusion period 12 months) in Flanders - Belgium were evaluated. RESULTS: There were 267 patients, Eastern Cooperative Oncology Group (ECOG) score was 2 in 24% and 0-1 in 76%. In 48%, two or more systemic regimens were given before nivolumab. The median overall survival was 7.8 months (95% confidence interval (CI) 6.3-9.3). At one year, the overall survival rate was 36.5±0.34%. Median progression-free survival was 3.7 months (95% CI 2.9-4.5). An objective response was obtained in 23.2%. ECOG score 2 and presence of liver metastasis strongly correlated with worse survival (p<0.00001). Treatment related adverse events grade 3 or 4 were reported in 21%, colitis (4%) and pneumonitis (7%) were most frequent. CONCLUSION: Upon implementation of nivolumab therapy in general hospitals, the case mix was characterized by a more heavily pretreated population with a substantial fraction of patients with ECOG score 2. The median overall survival is slightly inferior to what was published in the randomized phase III trials. An ECOG score 2 and the presence of liver metastasis correlated strongly with a worse survival. We report a high prevalence of serious adverse events.

Modern radiotherapy as part of combined modality treatment in locally advanced non-small cell lung cancer: present status and future prospects.

Locally advanced stages account for approximately one third of the incident presentations of non-small cell lung cancer (NSCLC). Optimal treatment in selected patients consists of an integration of chemotherapy and radiation therapy. Both modalities have seen numerous advances in the last decade. This article reviews the current status and outcome of treatment in stage III NSCLC, with special emphasis on the role of novel techniques in radiation treatment, including intensity-modulated radiation therapy. The obstacles for improving local control are identified and the technical progress that aims at removing these obstacles is addressed.

What is the optimal treatment of stage IIIA-N2 non-small-cell lung cancer after EORTC 08941?

The results of a randomized trial investigating the role of local therapies after induction chemotherapy in patients with stage IIIA-N2 non-small-cell lung cancer lend themselves to a review of the available evidence and speculation about the routine and future treatment in these patients. An algorithm for future treatment is proposed.

Titration procedures for nasal CPAP: automatic CPAP or prediction formula?

BACKGROUND: The best method for titration of continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) syndrome has not yet been established. The 90th or 95th percentiles of the pressure titrated over time by automatic CPAP (A-CPAP) have been recommended as reference for prescribing therapeutic fixed CPAP (F-CPAP). We compared A-CPAP to F-CPAP, which was determined by a common prediction formula. METHODS: Forty-five patients who were habituated to F-CPAP underwent titration polysomnography. In a double-blind, randomized order, each patient used an A-CPAP device in the autotitration and in the fixed pressure mode during one half of the night. Apnea-hypopnea index (AHI) and pressure profiles were primary outcomes. Bias and precision were additionally assessed for both CPAP modes. RESULTS: No significant differences in various sleep parameters or in subjective sleep quality evaluation were found. The AHI was effectively lowered in both CPAP modes (A-CPAP 7.7 [10.8]events/h versus F-CPAP 5.4 [9.0]events/h, p=0.061). Comparison of group means showed that F-CPAP closely paralleled mean (Pmean) and median (P50), but not the 95th percentile (P95) pressure, of A-CPAP. While bias was lowest for Pmean and P50, there was a lack of precision in all A-CPAP pressure categories. CONCLUSIONS: We confirm that F-CPAP set by prediction formula is not worse in terms of AHI control than A-CPAP. On average, F-CPAP parallels Pmean and P50 but not P95. However, due to imprecise matching, individual F-CPAP values cannot be derived from Pmean or P50.

Neoadjuvant chemotherapy in the treatment of nonsmall-cell lung cancer.

PURPOSE OF REVIEW: To review the recent evidence regarding the potential benefit on the outcome of neoadjuvant chemotherapy in patients with early-stage nonsmall-cell lung cancer and compare this evidence with the theoretical advantages and disadvantages of the approach. RECENT FINDINGS: The available evidence has mostly not yet been published in full manuscript form and should be interpreted cautiously. The observed gain in survival with neoadjuvant treatment is not consistent with expectations. Literature-based meta-analyses, however, estimate a gain in survival of at least 6% after 5 years. Neoadjuvant chemotherapy results in clinical downstaging in approximately 40-60% of the patients and pathological complete response rate in 5-10%. Neoadjuvant chemotherapy does not reduce the number of pneumonectomies. As expected, its compliance is better compared with adjuvant treatment. Neoadjuvant chemotherapy does not delay surgery or result in an increased hospital stay or rate of perioperative complications, when compared with immediate surgery. Neoadjuvant regimens should be platinum-based and at least three cycles of chemotherapy should be administered. SUMMARY: Neoadjuvant chemotherapy in early-stage nonsmall-cell lung cancer should not yet be offered outside of clinical trials and will in the future have to be compared with adjuvant chemotherapy.

Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis.

The authors report on a premenopausal female hemodialysis patient with relapsing pneumothorax, in whom the diagnosis of pulmonary lymphangioleiomyomatosis (LAM) was made. Ten years earlier, she had retroperitoneal bleeding from a kidney tumor corresponding to an angiomyolipoma (AML). The association between renal AML and pulmonary LAM is reviewed. Renal AML represents the most frequent extrapulmonary manifestation of pulmonary LAM. It is found in 32% to 60 % of cases in which a systematic search with abdominal computed tomography (CT) scan is done. The latter approach is advised to help avoid complications caused by renal AML. Therapeutic recommendations for renal AML are based on tumor size or presence of symptoms. Conversely, premenopausal women presenting with AML should be investigated for associated pulmonary LAM with high-resolution CT scan. Because LAM is very likely estrogen dependent, one of the several proposed antiestrogen therapies should be considered. Finally, there is significant overlap between renal AML, pulmonary LAM, and tuberous sclerosis. The latter should therefore be actively searched for in case of either AML or LAM.