Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel in early breast cancer: a retrospective analysis of 200 consecutive patients treated in a single center with a median follow-up of 9.5 years.

PURPOSE: We analyzed outcomes of doxorubicin-cyclophosphamide (AC) followed by weekly paclitaxel as neoadjuvant chemotherapy (NAC) for breast cancer (BC), in an everyday practice with long-term follow-up of patients. METHODS: All patients (n = 200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007 (n = 99); and subsequently every 2-week dose dense (dd) (n = 101). Clinical pathologic features, treatment course, and outcome information were recorded. Complete pathologic response (pCR) was analyzed according to BC subtype, dose regimen, and stage. RESULTS: Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human epidermal growth factor receptor-2 (HER2)-positive 32.5% (of whom 82% received trastuzumab), hormone receptor-positive/HER2-negative 53%, and triple negative 14.5%. Breast-conserving surgery (BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival (EFS) and overall survival (OS) are 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS. CONCLUSION: NAC for BC with AC-paclitaxel can be safely administered in the "real-world' setting with high efficacy. Current efforts are aimed at increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.

Similarity in activity and laterality patterns in the angular gyrus during autobiographical memory retrieval and self-referential processing.

Long-term memory is arguably one of the key cognitive functions. At the neural level, the lateral parietal cortex and the angular gyrus, particularly in the left hemisphere, exhibit strong activations during autobiographical and episodic memory retrieval. In a separate sub-field, left-lateralized activations of the angular gyrus are also found during self-referential processing, defined as higher activity when a trait term is judged by participants as being related to them vs. related to someone else. The question is whether episodic/autobiographical memory retrieval and self-referential processing effects are related. In the present study, thirty participants participated in the fMRI study with two separate experiments: autobiographical memory retrieval (Experiment 1) and self-referential processing (Experiment 2). In a series of analyses, including the most critical spatial correlation analysis between experiments, we found neural similarity between autobiographical memory retrieval and self-referential processing. Given that self-referential processing was identified in a selective way, the most plausible interpretation of our findings is that self-referential processing might partly explain the activation of the left angular gyrus during autobiographical memory retrieval. Our results are in line with the seminal view of Endel Tulving that the sense of self is a fundamental attribute of long-term memory recollection. However, it should be emphasized that: a) our results do not imply that the left angular gyrus is not involved in the retrieval of episodic memory details; and b) given that our experiment included an autobiographical memory task, generalization of our results to the episodic memory laboratory tasks has yet to be tested.

Naturalistic auditory stimuli with fNIRS prefrontal cortex imaging: A potential paradigm for disorder of consciousness diagnostics (a study with healthy participants).

Disorder of consciousness (DOC) is a devastating condition due to brain damage. A patient in this condition is non-responsive, but nevertheless might be conscious at least at some level. Determining the conscious level of DOC patients is important for both medical and ethical reasons, but reliably achieving this has been a major challenge. Naturalistic stimuli in combination with neuroimaging have been proposed as a promising approach for DOC patient diagnosis. Capitalizing on and extending this proposal, the goal of the present study conducted with healthy participants was to develop a new paradigm with naturalistic auditory stimuli and functional near-infrared spectroscopy (fNIRS) - an approach that can be used at the bedside. Twenty-four healthy participants passively listened to 9 min of auditory story, scrambled auditory story, classical music, and scrambled classical music segments while their prefrontal cortex activity was recorded using fNIRS. We found much higher intersubject correlation (ISC) during story compared to scrambled story conditions both at the group level and in the majority of individual subjects, suggesting that fNIRS imaging of the prefrontal cortex might be a sensitive method to capture neural changes associated with narrative comprehension. In contrast, the ISC during the classical music segment did not differ reliably from scrambled classical music and was also much lower than the story condition. Our main result is that naturalistic auditory stories with fNIRS might be used in a clinical setup to identify high-level processing and potential consciousness in DOC patients.

Functional near-infrared spectroscopy imaging of the prefrontal cortex during a naturalistic comedy movie.

Naturalistic stimulation (i.e., movies and auditory narratives of some minutes' length) has been a powerful approach to bringing more real-life experiences into laboratory experiments. Data-driven, intersubject correlation (ISC) analysis permits examining to what extent activity in a specific brain region correlates across participants during exposure to a naturalistic stimulus, as well as testing whether neural activity correlates with behavioral measures. Notably, most of the previous research with naturalistic stimuli was conducted using functional fMRI (fMRI). Here, we tested whether a naturalistic approach and the ISC are feasible using functional near-infrared spectroscopy (fNIRS) - the imaging method particularly suited for populations of patients and children. Fifty-three healthy adult participants watched twice a 3-min segment of a Charlie Chaplin movie while we recorded the brain activity on the surface of their prefrontal cortex using fNIRS. In addition, an independent group of 18 participants used a continuous scoring procedure to rate the extent to which they felt that different parts of the movie fragment were funny. Our two findings were as follows. First, we found higher-than-zero ISC in fNIRS signals in the prefrontal cortex lobes, a result that was particularly high in the oxygenated channels during the first repetition of the movie. Second, we found a significant negative correlation between oxygenated brain signals and ratings of the movie's humorousness. In a series of control analyses we demonstrated that this latter correlation could not be explained by various non-humor-related movie sensory properties (e.g., auditory volume and image brightness). The key overall outcome of the present study is that fNIRS in combination with the naturalistic paradigms and the ISC might be a sensitive and powerful research method to explore cognitive processing. Our results also suggest a potential role of the prefrontal cortex in humor appreciation.