Patterns and predictors of relapse in Merkel cell carcinoma: Results from a population-based study.

BACKGROUND AND PURPOSE: Prospective data evaluating the role of adjuvant radiotherapy (RT) for Merkel Cell Carcinoma(MCC) is lacking. To better understand the efficacy of adjuvant RT, a population-based patterns of failure study was conducted. METHODS: We identified MCC patients treated from 1988 to 2018.Primary outcome measures were recurrence-free survival (RFS), overall survival (OS) and MCC-specific survival (MCC-SS). Charlson Co-morbidity Index (CCI) was also calculated. RESULTS: 217 patients with mean age 79 (range: 33-96) were analyzed. The median follow-up was 40 months. Treatments were: surgery(S) alone (n = 101, 45%) or S + RT(n = 116, 55%).Local recurrence (LR) was low in stage I (n = 6, 6.5%) with clear margin of ≥1 cm, negative sentinel lymph node biopsy (SLNB) without high-risk factors, irrespective of adjuvant RT. Tumor size ≥ 2 cm (HR:2.95; p = 0.024) and immunosuppression(HR:3.98; p = 0.001) were associated with high risk of nodal failure. Adjuvant RT was associated with significant reduction in regional failure (HR:0.36; p = 0.002). Distant metastases (DM) were infrequent in stage I (4/90) and stage II (4/34), compared to stage III (32/93). Adjuvant RT improvedRFS but did not influence MCC-SS and OS. CCI was a significant predictor of OS. CONCLUSIONS: Adjuvant RT improvedRFS, withoutimpact on MCC-SS and OS. Co-morbidity rather than RT influenced OS. Adjuvant RT may be avoided instage I patients with negative SLNB and no associated high-risk factors. Prophylactic RNI could be considered in stage II with high risk features, inspite of negative SLNB. Stage III patients benefited from adjuvant RNI, but no impact on prevention of DM.

Concomitant Use of Proton Pump Inhibitors With Capecitabine Based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: Is it Safe?

AIM: Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC. METHODS: LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens. RESULTS: Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835). CONCLUSIONS: Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.

Squamous Cell Carcinoma of the Oral Tongue in Young Patients: Outcomes and Implications for Treatment.

Squamous cell carcinoma oral tongue (SCCOT) in patients below 45 years is relatively uncommon in literature; however, there have been increasing trends in incidence. Previous studies showed conflicting data, with no conclusive evidence of differences in outcome compared with older patients. The aim of our study was to determine if younger patients with tongue cancer in India had different clinico-pathological characteristics, prognostic determinants or survival than their older counterparts. Retrospective analysis of 425 adult patients of SCCOT, with 114 patients < 45 years of age (younger group) and 311 patients ≥ 45 years of age (older group), treated with surgery and adjuvant as indicated. Clinical and pathological features were described. Survival analysis was performed using Kaplan Meier's method and multivariate analysis was performed for recurrence and survival using Cox proportional hazards ratio. Younger patients had a higher incidence of adverse pathological features (APFs) like lymphovascular invasion (p = 0.01), perineural invasion (p = 0.009), poorer differentiation (p = 0.044), nodal involvement (p = 0.021), extranodal extension (p = 0.003) and local recurrence (p = 0.008). All of these factors were noted to impact survival. However, on multivariate analysis for APFs, age was not an independent predictor of recurrence or survival. Younger patients with squamous cell carcinoma of tongue have an increased risk of APFs and local recurrence. The clinical observation that young patients have a worse outcome is likely due to the association of APFs rather than age being an independent prognostic factor. Further study is required to show if tumour biology in this cohort is distinct.

A psychoacoustic method for studying the necessary and sufficient perceptual cues of American English fricative consonants in noise.

In a previous study on plosives, the 3-Dimensional Deep Search (3DDS) method for the exploration of the necessary and sufficient cues for speech perception was introduced (Li et al., (2010). J. Acoust. Soc. Am. 127(4), 2599-2610). Here, this method is used to isolate the spectral cue regions for perception of the American English fricatives /∫, 3, s, z, f, v, θ, δ in time, frequency, and intensity. The fricatives are analyzed in the context of consonant-vowel utterances, using the vowel /α/. The necessary cues were found to be contained in the frication noise for /∫, 3, s, z, f, v/. 3DDS analysis isolated the cue regions of /s, z/ between 3.6 and 8 [kHz] and /∫, 3/ between 1.4 and 4.2 [kHz]. Some utterances were found to contain acoustic components that were unnecessary for correct perception, but caused listeners to hear non-target consonants when the primary cue region was removed; such acoustic components are labeled "conflicting cue regions." The amplitude modulation of the high-frequency frication region by the fundamental F0 was found to be a sufficient cue for voicing. Overall, the 3DDS method allows one to analyze the effects of natural speech components without initial assumptions about where perceptual cues lie in time-frequency space or which elements of production they correspond to.

A psychoacoustic method to find the perceptual cues of stop consonants in natural speech.

Synthetic speech has been widely used in the study of speech cues. A serious disadvantage of this method is that it requires prior knowledge about the cues to be identified in order to synthesize the speech. Incomplete or inaccurate hypotheses about the cues often lead to speech sounds of low quality. In this research a psychoacoustic method, named three-dimensional deep search (3DDS), is developed to explore the perceptual cues of stop consonants from naturally produced speech. For a given sound, it measures the contribution of each subcomponent to perception by time truncating, highpass/lowpass filtering, or masking the speech with white noise. The AI-gram, a visualization tool that simulates the auditory peripheral processing, is used to predict the audible components of the speech sound. The results are generally in agreement with the classical studies that stops are characterized by a short duration burst followed by a F2 transition, suggesting the effectiveness of the 3DDS method. However, it is also shown that /ba/ and /pa/ may have a wide band click as the dominant cue. F2 transition is not necessary for the perception of /ta/ and /ka/. Moreover, many stop consonants contain conflicting cues that are characteristic of competing sounds. The robustness of a consonant sound to noise is determined by the intensity of the dominant cue.