Socioeconomic Status, Length of Stay, and Postoperative Complications in Oral Cavity Squamous Cell Carcinoma.

Background: Despite universal healthcare in Canada, low socioeconomic status (SES) has been associated with worse survival in oral cavity squamous cell carcinoma (OCSCC) patients. However, the relationship between SES and outcomes during the acute postoperative period is poorly defined. Hamilton, Ontario, presents a unique population with widely varying SES within the same geography. The objective of this study was to examine the relationship between SES, length of hospital stay (LOHS), and postoperative complications in OCSCC. Methods: Newly diagnosed OCSCC patients receiving primary surgical treatment from 2010 to 2014 were identified within a prospectively collected database. Inclusion criteria included age >18 years old, pathological diagnosis of oral cavity cancer, and primary surgical treatment with curative intent. Patients were excluded if they were undergoing palliative treatment or had previous head and neck surgery/radiotherapy. Postal codes were used to identify neighborhood-level socioeconomic variables via 2011 Canada Census data. Income quartiles were defined from groups of neighboring municipalities based on Canada Census definitions. Demographic, social, pathological, staging, and treatment data were collected through chart review. Results: One hundred and seventy-four patients were included in the final analysis. OCSCC patients with lower SES were more likely to be younger (P = .041), male (P = .040), have significant tobacco and alcohol use (P = .001), higher Charlson Comorbidity Index (CCI; P = .014), lower levels of education (P = .001), and have lower employment levels (P = .001). Lower SES patients had higher clinical tumor (P = .006) and clinical nodal (P = .004) staging and were more likely to receive adjuvant therapy (P = .001) and G-tubes (P = .001). Multivariable regression analysis showed that low SES was a statistically significant predictor of postoperative complications [ß 2.50 (95% confidence interval (CI) 0.200, 3.17); P = .014] and LOHS [ß 2.03 (95% CI 1.06, 2.99); P = .0001]. Tobacco and alcohol use, clinical tumor, and nodal stage, CCI, and planned adjuvant therapy were also statistically significant predictors of postoperative complications and LOHS (P < .05). Conclusion: Patients with lower SES have more advanced OCSCC disease with increased comorbidities that owes itself to more acute postoperative complications and LOHS within this study population. Patients with low SES should be identified as patients that require more support during their cancer treatment.

A phase 2 study of stereotactic body radiation therapy for squamous cell carcinoma of the head and neck (SHINE): a single arm clinical trial protocol.

BACKGROUND: Cancers of the head and neck region are often characterized by locally advanced, non-metastatic disease. Standard treatments for advanced cervico-facial cancers of the skin or primary head and neck squamous cell carcinoma (HNSCC) include combinations of surgery, radiation and chemotherapy, which are associated with high rates of acute toxicity and complications. Stereotactic body radiotherapy (SBRT) has been shown to be a promising modality of treatment for this patient population in retrospective studies; to our knowledge, there are no prospective clinical studies evaluating the safety and efficacy of SBRT in these patients. METHODS: This phase 2, single institution, single arm study aims to evaluate response rates to SBRT in older age patients with locally advanced HNSCC for whom primary surgery is not recommended or performed. The intervention is SBRT 45 Gy in 5 fractions given every 3-4 days. Toxicity, quality of life and patient outcomes will be recorded regularly up to 24 months after completion of SBRT. DISCUSSION: For this patient population, SBRT may offer a shorter and more effective treatment than the current standard of care palliative regimens. If the study demonstrates that SBRT is safe and effective, then this may lead to randomized studies comparing conventional radiotherapy to SBRT for selected head and neck cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04435938 .  Date registered: June 17, 2020.

Review of brachytherapy complications - Upper gastrointestinal tract.

While brachytherapy applications are not widely used for cancer diagnoses in the upper GI tract (including the esophagus, liver, stomach, and pancreas), they have a clear role in palliation and symptom management and occasionally definitive locoregional treatment. With the increasing use of image-guided techniques, the incidence of side effects and complications has shown to be lower than many other alternative treatment modalities, making brachytherapy approaches a preferred treatment option. This review examines procedural complications and acute and chronic adverse effects from radiation associated with esophageal, hepatobiliary, and pancreatic brachytherapy and their management.

Trends in Reporting of Swallowing Outcomes in Oropharyngeal Cancer Studies: A Systematic Review.

Over the last two decades, dysphagia is increasingly recognized as a significant short-term and long-term issue in oropharyngeal cancer patients. However, there remains a lack of standardization and agreement about reporting swallowing outcomes in studies that assess treatment outcomes in this population. A systematic review was performed following PRISMA Guidelines by searching Pubmed (MEDLINE) and Scopus. The inclusion criteria used included (1) prospective and retrospective clinical studies involving adult patients with oropharyngeal cancer, (2) reports swallowing outcomes, (3) English studies or studies with English translation, (4) full text retrievable and (5) publication between 1990 and 2016. 410 unique studies were identified, and 106 were analyzed. A majority (> 80%) of studies that reported swallowing outcomes were published after 2010. While 75.4% of studies reported subjective outcomes (e.g., patient-reported or clinician-reported outcome measures), only 30.2% of studies presented results of objective instrumental assessment of swallowing. The majority (61%) of studies reported short-term swallowing outcomes at 1 year or less, and only 10% of studies examined 5-year swallowing comes. One study examined late-dysphagia (> 10 years) in the oropharyngeal cancer population. Considerable heterogeneity remains in the reporting of swallowing outcomes after treatment of oropharyngeal cancer despite its importance for quality of life. Studies reporting long-term swallowing outcomes are lacking in the literature, and objective measures of swallowing function remain underutilized and nonstandardized.

Head and Neck Cancer Survivorship Care: A Review of the Current Guidelines and Remaining Unmet Needs.

OPINION STATEMENT: A larger proportion of patients with head and neck cancers (HNC) are now surviving, constituting up to 3% of all cancer survivors. This is likely due in part to the increase in HPV-related oropharyngeal cancers affecting younger individuals and with a better prognosis and to the improved outcomes of other HNCs as well over the last two decades. Most studies have previously been focusing on improving risk stratification, treatment and disease-related outcomes. Over the last decade, there has been an evolving interest in the field of survivorship care. Despite the collaborative efforts from a multidisciplinary team in managing cancer and treatment-related side-effects and in improving survivors' overall quality of life (QOL), it has been reported that up to 60-65% of patients have at least one unmet need. The purpose of this article is to review current guidelines for HNC survivorship care and identify areas of unmet need. Over the last 5 years, multiple groups have published guidelines describing survivorship care issues and their possible management. Although a very comprehensive and informative first initiative, multiple issues need to be further evaluated. These include how to best support patients and their partners' fear of cancer recurrence, to provide coordinated care among all physicians, to identify and meet patients' needs in local multidisciplinary teams and to institute measures to ensure every individual's access to high-quality patient-centred care. Furthermore, experts may consider engaging in further dialog with primary care physicians (PCP) to improve sharing of survivorship care. More should be learned about PCPs' comfort levels in providing such care and whether further steps are required to facilitate a seamless. Transition of care and accessibility to specialized care as needed.

A Case of Sinonasal Undifferentiated Carcinoma with Brain Metastases.

Sinonasal undifferentiated carcinoma (SNUC) is a rare aggressive neoplasm arising in the nasal cavity and paranasal sinuses. We report a unique case of an 80-year-old man who presented with a locally advanced SNUC involving the ethmoid, sphenoid, and maxillary sinuses and bilateral lymph nodes, clinical T4N2M0. Given his age and the initial extent of his primary tumour, he was treated with neoadjuvant chemotherapy followed by chemoradiation with a split course of 50 Gray (Gy) in 40 fractions delivered twice a day. Four months after his treatments, he developed a recurrence at the left lower eyelid and left frontal sinus, intrabdominal metastases, and a left cerebellar metastasis. A single fraction of 22 Gy was delivered to the cerebellar lesion using stereotactic radiosurgery. He survived 17 months from the initial presentation. We review the available literature regarding treatment of brain metastases and use of hyperfractionated radiotherapy in this rare head and neck cancer.

In a Heartbeat: An Assessment of Dynamic Dose Variation to Cardiac Structures Using Dual Source Computed Tomography.

PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition. The WH, LV, LMCA, and proximal, middle, and distal LAD segments were contoured on each phase of the cardiac cycle. The maximum, minimum, and mean Hausdorff distance between each structure and the tangential fields was assessed in ventricular systole and diastole. Four-dimensional dose-volume histograms were used to compare the systolic and diastolic dosimetric data. RESULTS: Ten patients were enrolled. The average maximum, minimum, and mean Hausdorff distance variation from systole to diastole was ≤4 mm for the LV and LMCA and ≤3 mm for the WH and LAD segments. WH maximum dose and volume receiving 5 Gy were decreased in systole compared with diastole (42.9 Gy versus 44.5 Gy, P = .03, and 21.7 cm3 versus 27.7 cm3, P = .01), but the mean dose remained similar throughout the cycle. The maximum and mean dose to the distal LAD was 21.2 Gy versus 26.6 Gy (P = .005) and 8.6 Gy versus 13.2 Gy (P = .006) in systole versus diastole, respectively. The maximum and mean dose to the middle LAD was 18.4 Gy versus 25.1 Gy (P = .005) and 8.5 Gy versus 10.2 Gy in systole versus diastole (P = .005). The maximum dose to the LV was lower in systole than in diastole (21.5 Gy vs 26.7 Gy; P = .005). CONCLUSIONS: In addition to deep-inspiration breath-hold, systolic irradiation is associated with a reduction in dose to the LAD, LV, and WH. In addition to its potential use in radiation planning for cardiac gating, DSCT imaging can be used to help define a planning organ at risk volume for clinically important cardiac substructures.

A Novel Neoadjuvant Therapy for Operable Locally Invasive Non-Small-Cell Lung Cancer. Phase I Study of Neoadjuvant Stereotactic Body Radiotherapy. LINNEARRE I (NCT02433574).

BACKGROUND: Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non-small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined. We hypothesized that a short course of preoperative SBRT is feasible and can be delivered safely as a neoadjuvant therapy in patients at risk for incomplete resection. METHODS: In this phase I study, 20 patients with cT3 to 4, N0 to 1, M0 NSCLC at risk for incomplete resection will be treated with neoadjuvant SBRT followed by surgery and adjuvant chemotherapy. Four groups of 5 patients will be treated with escalating doses (35, 40, 45, and 50 Gy) in 10 daily fractions. The primary outcome is feasibility (ie, the ability to complete SBRT and surgery as planned; within 7 weeks). Secondary outcomes include acute and late adverse events; R0, R1, and R2 rates; and secondary surrogates of feasibility and safety. RELEVANCE: This study is an important first step in introducing a new therapeutic modality to patients with LA NSCLC that could improve surgical outcomes in the future. If neoadjuvant SBRT is found to be feasible and safe for LA NSCLC, its effect in achieving R0 resection could be investigated in randomized trials.

Analysis of Pulmonary Vein Antrums Motion with Cardiac Contraction Using Dual-Source Computed Tomography.

PURPOSE: The purpose of the study was to determine the extent of displacement of the pulmonary vein antrums resulting from the intrinsic motion of the heart using 4D cardiac dual-source computed tomography (DSCT). METHODS: Ten consecutive female patients were enrolled in this prospective planning study. In breath-hold, a contrast-injected cardiac 4-dimensional (4D) computed tomography (CT) synchronized to the electrocardiogram was obtained using a prospective sequential acquisition method including the extreme phases of systole and diastole. Right and left atrial fibrillation target volumes (CTVR and CTVL) were defined, with each target volume containing the antral regions of the superior and inferior pulmonary veins. Four points of interest were used as surrogates for the right superior and inferior pulmonary vein antrum (RSPVA and RIPVA) and the left superior and inferior pulmonary vein antrum (LSPVA and LIPVA). On our 4D post-processing workstation (MIM Maestro™, MIM Software Inc.), maximum displacement of each point of interest from diastole to systole was measured in the mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions. RESULTS: Median age of the enrolled patients was 60 years (range, 56-71 years). Within the CTVR, the mean displacements of the superior and inferior surrogates were 3 mm vs. 1 mm (p=0.002), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 0 mm (p=0.00001), in the ML, AP, and SI directions, respectively. On the left, mean absolute displacements of the LSPVA vs. LIPVA were similar at 4 mm vs. 1 mm (p=0.0008), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 1 mm (p=0.00001) in the ML, AP, and SI directions. CONCLUSION: When isolated from breathing, cardiac contraction is associated with minimal inferior pulmonary veins motion and modest (1-6 mm) motion of the superior veins. Target deformation was thus of a magnitude similar or greater than target motion, limiting the potential gains of cardiac tracking. Optimal strategies for cardiac radiosurgery should thus either incorporate the generation of an internal target or cardiac gating. In either case, cardiac 4D DSCT would allow for personalized margin definition.

Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

BACKGROUND: Despite the promise of metabolic tumor volume (MTV) as a risk-stratifying marker, the retrospective design of the initial study limits its generalizability. Therefore, this study sought to validate MTV as a prognostic factor for oral cavity squamous cell carcinoma (OCSCC) treated with primary surgery within an independent data set. METHODS: The validation data set consisted of 42 patients diagnosed with OCSCC between 2008 and 2012. The original cohort consisted of 80 patients. MTV and SUVmax were calculated for the primary tumor and nodal metastasis separately, as well as combined. Before statistical analysis, MTV and SUVmax values were divided into intertertile thirds to allow for intergroup survival analysis. Validation analysis was conducted on the validation data set alone. Data from both cohorts were then combined (n=122) to increase statistical power. RESULTS: An increase in combined MTV of 17.5cm(3) was associated with statistically significant increase in risk of disease recurrence (HR=19.2, p<0.001) and death (HR=9.2, p<0.05). Combined SUVmax failed to predict overall (HR=1.0, p>0.05) and disease-free survival (HR=1.0, p>0.05). Increase in the MTV of the primary tumor was associated with an increase in the risk of disease recurrence (HR=21.7, p=0.0001) and risk of death (HR=7.0, p=0.0001), while increase in the MTV of the locoregional neck metastasis was not (p>0.05). An MTV cutoff value of greater than 10.2cm(3) was found to significantly affect survival. CONCLUSION: Due to the reproducibility of MTV findings, this study validates MTV as an independent prognostic factor for OCSCC treated with primary surgery.

Optimal detection of hypothyroidism in early stage laryngeal cancer treated with radiotherapy.

BACKGROUND: Hypothyroidism following radiation therapy (RT) for treatment of Head and Neck Cancer (HNC) is a common occurrence. Rates of hypothyroidism following RT for Early Stage Laryngeal Squamous Cell Carcinoma (ES-LSCC) are among the highest. Although routine screening for hypothyroidism is recommended; its optimal schedule has not yet been established. We aim to determine the prevalence and optimal timing of testing for hypothyroidism in ES-LSCC treated with RT. METHOD: We conducted a population-based cohort study. Data was extracted from a prospective provincial head and neck cancer database. Demographic, survival data, and pre- and post-treatment thyroid stimulating hormone (TSH) levels were obtained for patients diagnosed with ES-LSCC from 2008-2012. Inclusion criteria consisted of patients diagnosed clinically with ES-LSCC (T1 or 2, N0, M0) treated with curative intent. Patients were excluded if there was a history of hypothyroidism before the treatment or any previous history of head and neck cancers. RESULTS: Ninety-five patients were included in this study. Mean age was 66.1 years (range: 44.0-88.0 years) and 82.3% of patients were male. Glottis was the most common subsite at 77.9% and the average follow-up was 40 months (Range: 12-56 months). Five-year overall survival generated using the Kaplan-Meier method was 79%. Incidence of hypothyroidism after RT was found to be 46.9%. The greatest frequency of developing hypothyroidism was at 12 months. CONCLUSIONS: We found a high prevalence of hypothyroidism for ES-LSCC treated with RT, with the highest rate at 12 months. Consequently, we recommend possible routine screening for hypothyroidism using TSH level starting at 12 months. To our knowledge, this is the first study to suggest the optimal timing for the detection of hypothyroidism.

Long-term Survival in a Patient with Metastatic Spinal Cord Compression from a Prostate Cancer with Ultra-high PSA: Case Report and Review of the Literature.

A 77-year-old man presented to the hospital for non-ambulation of 48 hours prior to admission.  He was found to have a metastatic spinal cord compression (MSCC), a PSA exceeding 27,000, and biopsy-confirmed prostate cancer. After palliative radiation (RT) to the spine and medical treatment, the patient recovered his functions fully and survived for more than 7.5 years, far beyond what would be expected based on current published literature.  A systematic review of the literature of MSCC in patients with prostate cancer was carried out. Prognostic factors of ambulation after RT included pre-treatment neurological status, duration of neurological deficits, and severity of the neurological impairment. Positive predictive factors of local control included single level of metastasis, time of development of motor deficits of more than 14 days, no prior androgen-deprivation therapy (ADT), age under 65, and longer course of RT (10 fractions of 2 Gy). Absence of prior ADT, pre-treatment ambulation, a single site of metastasis, and haemoglobin of less than 12g/L were positive predictors for survival.

Endotracheal brachytherapy alone: An effective palliative treatment for tracheal tumors.

BACKGROUND: Tracheal tumors are rare. They are usually unresectable and treated primarily with external beam radiation. The use of palliative endotracheal brachytherapy (ETBT) alone in treating patients with tracheal tumors has not been reported. METHODS: Using a prospective database, demographic, treatment, and outcome data of patients with tracheal tumors treated palliatively with ETBT from 2006 to 2014 were analyzed. Tumor and symptom responses were evaluated based on response evaluation criteria in solid tumors criteria. Survival, in-field disease control, symptom response, and duration of symptom responses were evaluated using descriptive analyses. RESULTS: Sixteen ETBT (median, 2) treatments were delivered to 8 patients. Median age was 63.4 years old. Common symptoms were hemoptysis, cough, and dyspnea. Tracheal lengths of 3.5-11 cm were treated with 5-7 Gy/fraction, using 1-3 fractions. The mean overall survival was 5 months and symptom-free survival was 6.8 months, respectively. After ETBT, 88% of patients experienced symptomatic improvement (hemoptysis [n = 3/3], cough [n = 6/7], and dyspnea [n = 4/4]). One patient developed Grade 1 stenosis that did not require intervention. CONCLUSIONS: This is among the largest series of tracheal tumors treated palliatively with ETBT alone. ETBT provided effective palliation with symptom improvement and minimal toxicity.

Turn down the noise--a blinded evaluation of iterative image reconstruction in radiation therapy computed tomography simulation.

PURPOSE: The current standard reconstruction algorithm for computed tomography (CT) scans is filtered back projection. Alternative algorithms using iterative reconstruction (IR)-in our case, "sinogram affirmed iterative reconstruction"-have been increasingly implemented in diagnostic CT imaging. We studied its potential in improving radiation therapy planning images. METHODS AND MATERIALS: Raw planning CT data sets of patients from varied disease sites were reconstructed using filtered back projection and IR levels 1, 3, and 5 with equal radiation dose. For each site, 2-7 patient scans were selected; 2-3 physicians blindly evaluated the 4 3-dimensional image sets. Using a visual analogue scale, they rated the sharpness, noise, perceived ease in delineating gross tumor/clinical target volume and organs at risk, and overall appreciation of the images. Interobserver correlation was calculated with the Spearman correlation coefficient (ρ). Generalized estimating equations assessed the differences in the mean score for each criterion between reconstructions. When significant differences existed, pairwise comparisons compared the least-squares means. The preference for each reconstruction was rank ordered for each observer. The rank occurrences were computed; generalized estimating equations and pairwise comparisons were again calculated. RESULTS: Sixteen physicians reviewed 548 image sets. The sharpness had a ρ = -0.22-0.53, noise ρ = -0.34-0.38, delineating gross tumor/clinical target volume ρ = -0.28-0.53, delineating organs at risk ρ = -0.47-0.42, and overall appreciation ρ = -0.17-0.38, suggesting a low level of agreement among observers. IR 3 and 5 had consistently higher scores and ranks than filtered back projection (P = .02 and P = .015, respectively). Paradoxically, IR 5 scored both highest and worst the most frequently. IR 3 was more consistently well-ranked for all criteria. CONCLUSIONS: This report is the first to clinically evaluate IR in radiation therapy planning. When used to reduce noise in current CT simulation protocols, IR images were generally preferred. Although highly processed images polarized observers, the use of moderate IR was appreciated for most disease sites.

Skin elasticity as a measure of radiation fibrosis: is it reproducible and does it correlate with patient and physician-reported measures?

Current means of measuring RT-induced fibrosis are subjective. We evaluated the DermaLab suction cup system to measure objectively skin deflection as a surrogate for fibrosis. Sixty-nine patients with E-STS were treated with limb-sparing surgery and 50-66 Grays (Gy) of RT. Using a "scleroderma" DermaLab Suction Cup, the skin stiffness was measured by two clinicians. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale, the Musculoskeletal Tumor Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) questionnaires were completed for each patient. Levels of agreement between measurers were estimated using the Kappa (k) coefficient and the concordance correlation coefficient (CCC). All sixty-nine patients were included. The level of agreement between measurers for NCI-CTCAE grading was moderate (range k = 0.41-0.59). The CCC for the elasticity measurements were higher, with CCC = 0.82 for fibrotic skin and CCC 5 0.84 for normal skin. The elasticity measurements were significantly higher when MSTS scores were <30 and or TESS scores were <90. Suction Cup measurement of skin elasticity is more reproducible than CTCAE grading and shows promise in generating reproducible measurements for radiation-induced skin fibrosis. Furthermore, it correlates well with the MSTS and TESS.

Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission.

The pathophysiological neural mechanism underlying the depressogenic and anxiogenic effects of chronic adolescent cannabinoid use may be linked to perturbations in monoaminergic neurotransmission. We tested this hypothesis by administering the CB(1) receptor agonist WIN55,212-2, once daily for 20 days to adolescent and adult rats, subsequently subjecting them to tests for emotional reactivity paralleled by the in vivo extracellular recordings of serotonergic and noradrenergic neurons. Chronic adolescent exposure but not adult exposure to low (0.2 mg/kg) and high (1.0 mg/kg) doses led to depression-like behaviour in the forced swim and sucrose preference test, while the high dose also induced anxiety-like consequences in the novelty-suppressed feeding test. Electrophysiological recordings revealed both doses to have attenuated serotonergic activity, while the high dose also led to a hyperactivity of noradrenergic neurons only after adolescent exposure. These suggest that long-term exposure to cannabinoids during adolescence induces anxiety-like and depression-like behaviours in adulthood and that this may be instigated by serotonergic hypoactivity and noradrenergic hyperactivity.

Decline in serotonergic firing activity and desensitization of 5-HT1A autoreceptors after chronic unpredictable stress.

Chronic stressful life events are risk factors for contracting depression, the pathophysiology of which is strongly associated with impairments in serotonergic (5-HT) neurotransmission. Indeed, in rodents, exposure to chronic unpredictable stress (CUS) produces depressive-like behaviours such as behavioural despair and anhedonia. To date, there have not been many studies that especially explore in vivo changes in 5-HT neurotransmission associated with CUS in the rat. Therefore, using in vivo electrophysiology, we evaluated whether CUS that induces anhedonia-like behaviours concurrently impairs midbrain raphe 5-HT neuronal activity. Unlike unstressed and acutely stressed rats, CUS produced progressive reductions in sucrose intake and preference (anhedonia-like). These were associated with a decrease in the spontaneous firing activity (35.4%) as well as in the number of spontaneously active 5-HT neurons, and a desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal raphe. These results suggest that CUS dramatically decreases 5-HT neural activity and 5-HT1A autoreceptor sensitivity, and may represent endophenotypic features of depressive-like states.