Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Monday, November 23, 2020

Long-term Oncologic Impact of Positive Anterior and Posterior Surgical Margins After Radical Prostatectomy

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imageObjective: The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer. Patients and Methods: We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model. Results: There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed. Conclusions: In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.
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Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016

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imageBackground: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. Methods: Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. Results: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P
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Comparing Late-line Treatment Sequence of Regorafenib and Reduced-intensity FOLFOXIRI for Refractory Metastatic Colorectal Cancer

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No abstract available
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Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database

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imageObjectives: Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs. Materials and Methods: We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival. Results: We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. 120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs.
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Effect of Age on Cancer-specific Mortality in Patients With Urothelial Carcinoma of the Urinary Bladder: A Population-based Competing-risks Analysis Across Disease Stages

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imageObjective: The objective of the study is to test the effect of age on cancer-specific mortality (CSM) in patients with urothelial carcinoma of the urinary bladder (UCUB), across all disease stages. Materials and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016), we identified 207,714 patients. Age was categorized as: below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above. Multivariable competing-risks regression (CRR) models were used according to disease stage (low-risk nonmuscle invasive: TaN0M0 low grade, high-risk nonmuscle invasive: Ta high grade or Tis-1N0M0, muscle invasive: T2-3N0M0, regional: T4N0M0/TanyN1-3M0, and metastatic: TanyNanyM1). Results: Overall, 33,970 (16.4%) versus 52,173 (25.1%) versus 64,537 (31.1%) versus 57,034 (27.4%) patients were below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above, respectively. In multivariable CRR models that focused on low-risk nonmuscle invasive UCUB, advanced age was associated with higher CSM rates (hazard ratio [HR]: 7.04 in patients aged 80 y and above, relative to below 60 y; P
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Brain Radiation Induced Extracranial Abscopal Effects in Metastatic Melanoma

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imageHistorically, the brain has been viewed as a specialized neurovascular inert organ with a distinctive immune privilege. Therefore, radiation-induced extracranial abscopal effects would be considered an unusual phenomenon due to the difficulty of the immunogenic signaling molecules to travel across the blood-brain barrier (BBB). However, it is now possible that localized central nervous system radiation has the ability to disrupt the structural integrity of the BBB and increase its endothelial permeability allowing the free passage of immunogenic responses between the intracranial and extracranial comp artments. Thus, the nascent tumor–associated antigens produced by localized brain radiation can travel across the BBB into the rest of the body to modulate the immune system and induce extracranial abscopal effects. In clinical practice, localized brain radiation therapy–induced extracranial abscopal effects are a rarely seen phenomenon in metastatic melanoma and other advanced cancers. In this article, we provide a detailed overview of the current state of knowledge and clinical experience of central nervous system radiation–induced extracranial abscopal effects in patients with malignant melanoma. Emerging data from a small number of case reports and cohort studies of various malignancies has significantly altered our earlier understanding of this process by revealing that the brain is neither isolated nor passive in its interactions with the body's immune system. In addition, these studies provide clinical evidence that the brain is capable of interacting actively with th e extracranial peripheral immune system. Thus, localized radiation treatment to 1 or more locations of brain metastases can induce extracranial abscopal responses. Collectively, these findings clearly demonstrate that localized brain radiation therapy–induced abscopal effects traverses the BBB and trigger tumor regression in the nonirradiated extracranial locations.
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Adjuvant Trastuzumab Emtansine (T-DM1) and Concurrent Radiotherapy for Residual Invasive HER2-positive Breast Cancer: Single-center Preliminary Results

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imageObjectives: The treatment of nonmetastatic HER2-positive breast cancer with residual invasive disease using concurrent Trastuzumab emtansine (T-DM1) and radiotherapy appears to be an effective option. Our aim was to evaluate the acute side effects of this treatment regime. Methods: Fourteen patients were treated between March 2019 and April 2020 concurrent T-DM1 and radiotherapy. Left ventricular ejection fraction was assessed at baseline, before and after radiotherapy. All toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 3.0. Results: The median age was 55 years (range 36 to 72). All patients received total dose of 50 Gy for the breast/ chest wall, 10 patients got lymph node irradiation, 4 patients received an additional tumor bed boost. The most common side effect was grade 1 radiodermatitis. A reversible grade 2 left ventricular ejection fraction decrease occurred in 2 patients. During our examination 3 patients showed alanine aminotransferases increase after the cycle 4 of T-DM1, 1 patient had grade 1, 1 patient grade 2, and 1 patient grade 3 alanine aminotransferase increases. Conclusions: The acute toxicity rate especially focusing on skin and cardiac toxicity were assumed acceptable in our cohort. To safely administer this concomitant treatment, further examination and prospective data are needed.
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SBRT in non-spine bone metastases: a literature review

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Abstract

Stereotactic Body Radiotherapy (SBRT) is a technique for delivering high doses of radiation to tumors while preserving the normal tissues located around this area. Bone metastases are frequent in cancer patients. They can be distressingly painful or may cause pathological fractures. Radiation therapy is a fundamental aspect of treatment for bone metastases. The objective of this study is to analyze the literature on non-spine bone metastasis treated with SBRT, including immobilization, volume delineation, dose and fractionation, local control, side effects, and assessment of response after treatment. Full-text articles written in English language and published in the last 10 years were included in this review and were accessible on PubMed and MEDLINE. We examined 78 articles. A total of 40 studies were included in this review. Most were retrospective studies. The articles included were evaluated for content and validation. The immobilization systems and imaging tests used for tumor delimitation were variable between studies. The use of CTV (Clinical Target Volume) has not been defined. Doses and fractions were variable from 15 to 24 Gy/1 fraction to 24–50 Gy in 3–5 fractions, with local control being around 90% with a low rate of side effects. We review state of the art in SBRT non-spine metastases. SBRT can result in better local control and pain management in non-spine bone metastases patients. We need more research in volume delineation determining whether or not to use CTV and the role of MRI in volume contouring, optimal doses, and fractionation according to histology and a reliable response assessment tool. Studies that compare SBRT to conventional radiotherapy in local control and pain control are needed.

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Validity and reliability of the MD Anderson dysphagia inventory in English and Chinese in head and neck cancer patients

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Abstract

Aims

Patient‐reported outcome measures are important in assessing the impact of dysphagia on quality of life. Our aim was to adapt and examine the cultural validity and reliability of a swallowing‐related quality of life measure, the MD Anderson Dysphagia Inventory (MDADI), in English and Chinese, with head and neck cancer patients.

Methods

We adapted the MDADI to Chinese through formal forward‐backward translation. Sixty‐six head and neck cancer survivors completed the MDADI, Swallowing Quality of Life (SWAL‐QOL) questionnaire and Hospital Anxiety and Depression Scale (HADS) in English or Chinese. Swallowing status was scored on the Functional Oral Intake Scale (FOIS). Seventy‐four percent (n = 49) of participants completed a repeat administration of the MDADI for test–retest reliability analysis.

Results

The MDADI showed high internal consistency reliability (Cronbach's α , 0.82 ≤ α ≤ 0.94), and test–retest reliability in both English (intraclass correlation coefficient, ICC = 0.81) and Chinese (ICC = 0.72). Criterion validity was established through moderate to strong correlations with relevant SWAL‐QOL domains. Convergent validity was determined by significant correlations to the HADS and FOIS. Divergent validity was determined by nonsignificant association to the SWAL‐QOL Sleep domain. The MDADI also presented as hypothesised to most known‐group theoretical constructs.

Conclusions

The MDADI showed good psychometric properties in English and Chinese. This avails a reliable and psychometrically valid MDADI for Chinese speakers.

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Somatic Epigenetic Silencing of RIPK3 Inactivates Necroptosis and Contributes to Chemoresistance in Malignant Mesothelioma.

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CONCLUSIONS: These data suggest that RIPK3 acts as a tumor suppressor in MM by triggering necroptosis and that epigenetic silencing of RIPK3 by DNA methylation impairs necroptosis and contributes to chemoresistance and poor survival in this incurable disease. PMID: 33203643 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
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Entinostat plus pembrolizumab in patients with metastatic NSCLC previously treated with anti-PD-(L)1 therapy.

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CONCLUSIONS: In anti-PD-(L)1-experienced NSCLC patients, entinostat plus pembrolizumab did not achieve the primary response rate endpoint but provided a clinically meaningful benefit with objective response in 9% of patients. No new toxicities, including immune-related adverse events, were seen for either drug. Future studies will continue to evaluate the association of monocyte levels and response. PMID: 33203644 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
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Meta-analysis of laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma

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AbstractIntrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive hepatic malignancy. An up-to-date systematic review and meta-analysis was conducted aiming to compare outcomes between laparoscopic (LLR) and open liver resection (OLR) for patients with iCCA. A systematic literature search of Medline, Scopus, Google Scholar, and Cochrane databases was performed. A total of 8 studies comprising 2872 patients, who underwent LLR or OLR for iCCA, were included in our meta-analysis. LLR patients had smaller tumors [mean difference (MD): − 1.17 cm, 95% confidence intervals (CI) − 1.77 to − 0.57,p = 0.0001], underwent major resections less frequently [risk ratio (RR): 0.75, 95% CI 0.67–0.83,p <  0.00001] and R0 resections more frequently (RR: 1.05, 95% CI 1.01–1.0...
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