Publications by authors named "Luca Valle"

32 Publications

National variation in the delivery of radiation oncology procedures in the non-facility-based setting.

Cancer Med 2021 Jul 2;10(14):4734-4742. Epub 2021 Jun 2.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA.

Purpose: Though utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics.

Methods: The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non-facility-based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT).

Results: In total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58-26.05, p < 0.001), but not greater delivery of other technologies. Metropolitan practice was the only predictor for greater HDR brachytherapy utilization (OR 12.95, 95% CI 1.81-92.60, p = 0.01). Practice region was predictive of the delivery of 3DCRT, SRS and SBRT (p < 0.01, p < 0.001, and p < 0.001, respectively). With the Northeast as the reference region, 3DCRT was more likely to be delivered by providers in the South (OR 1.33, 95% CI 1.09-1.62, p < 0.01) and the West (OR 1.38, 95% CI 1.11-1.71, p < 0.01). At the same time, SRS use was less likely in the Midwest (OR 0.71, 95% CI 0.55-0.91, p < 0.01), South (OR 0.49, 95% CI 0.40-0.61, p < 0.001), and West (OR 0.43, 95% CI 0.34-0.55, p < 0.001). SBRT, on the other hand, was more commonly utilized in the Midwest (OR 2.63, 95% CI 1.13-6.13, p = 0.03), South (OR 3.44, 95% CI 1.58-7.49, p < 0.01), and West (OR 4.87, 95% CI 2.21-10.72, p < 0.001). HDR brachytherapy use was also more likely in the Midwest (OR 1.97, 95% CI 1.11-3.49, p = 0.02) and West (OR 1.87, 95% CI 1.08-3.24, p = 0.03). While the degree held by the billing physician did not predict for delivery of a given procedure, greater years since graduation was related to decreased likelihood of SBRT use (OR 0.98, 95% CI 0.96-0.99, p < 0.001) and increased likelihood of LDR brachytherapy use (OR 1.02, 95% CI 1.00-1.04, p = 0.02).

Conclusions: Substantial geographic variation in the use of specific RT technologies was identified. The degree to which this variation reflects effective care, preference-sensitive care, or supply-sensitive care warrants further investigation.
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http://dx.doi.org/10.1002/cam4.4028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290244PMC
July 2021

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

Eur Urol 2021 Aug 10;80(2):142-146. Epub 2021 May 10.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.04.035DOI Listing
August 2021

Reply to Sungeun Kim, Jae Il Shin, and Jonathan Evan Shoag's Letter to the Editor re: Luca F. Valle, Eric J. Lehrer, Daniela Markovic, et al. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.11.010.

Eur Urol 2021 Jul 29;80(1):e15-e16. Epub 2021 Apr 29.

Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.04.010DOI Listing
July 2021

Methods for restoration of ki67 antigenicity in aged paraffin tissue blocks.

Histochem Cell Biol 2021 Apr 10. Epub 2021 Apr 10.

Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, IRCCS AOU San Martino IST, Largo Rosanna Benzi, 10, 16132, Genoa, Italy.

Pathology archives are a treasure trove of paraffin embedded tissue spanning many years and covering a wide variety of tissues and diseases. The possibility of using old archival formalin fixed paraffin embedded (FFPE) tissues for diagnostic updates and research projects is a widespread need and it requires archives of stable, well-preserved samples. Immunohistochemistry performed on old archival paraffin blocks may give unreliable results, in particular for some antigens, such as Ki67. In consideration of this phenomenon, our aim is to comprehensively test and identify methods which may be used to obtain Ki67 immunohistochemical reactions of good quality from old archival FFPE blocks. Various methods were tested in order to evaluate their possible efficacy in increasing Ki67 immunointensity in a collection of 40-year-old, archival blocks including re-embedding, with deeper sectioning of tissue from the block and increasing heat-based pretreatment times (20 cases) and re-processing (20 cases). All reactions were performed using an automated immunostainer and Ki67 stained immunosections compared using a visual colour-based scale (the first immunostained section was considered as baseline). The combination of deep sectioning (1000 µM) and prolonged heat-based pretreatment (64 min) markedly increased immunoreactivity for Ki67. Re-embedding and reprocessing did not have a significant effect. Large tissue samples showed heterogeneity of Ki67 immunoexpression between the periphery of the sample and the central area. In conclusion, the study defines a useful protocol to increase antigen retrieval applicable to dated archival tissues.
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http://dx.doi.org/10.1007/s00418-021-01987-wDOI Listing
April 2021

Use and Impact of Positron Emission Tomography/Computed Tomography Prior to Salvage Radiation Therapy in Men with Biochemical Recurrence After Radical Prostatectomy: A Scoping Review.

Eur Urol Oncol 2021 Jun 24;4(3):339-355. Epub 2021 Feb 24.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Context: The use, common findings, and impact of modern molecular positron emission tomography (PET)/computed tomography (CT) imaging prior to salvage radiation therapy (RT) in men with biochemical recurrence after radical prostatectomy (RP) have not been evaluated comprehensively.

Objective: We performed a scoping systematic review of the literature assessing detection rates, detection patterns, changes in management, as well as changes in patient outcome resulting from molecular PET/CT imaging using three molecular tracers: F-fluciclovine, Ga prostate-specific membrane antigen (PSMA)-11, and F-DCFPyL.

Evidence Acquisition: A computerized bibliographic search of the Medline/PubMed database was carried out from inception to October 1, 2020. We included published reports and abstracts evaluating the utility of Fluciclovine, Ga-PSMA-11, and F-DCFPyL PET in the detection of recurrent disease in the post-RP, pre-salvage RT setting. Outcomes of interest were extracted and tabulated, and existing evidence was synthesized qualitatively.

Evidence Synthesis: A total of 45 studies were included in our qualitative synthesis. Detection rates were high across most studies, and there was often a clear relationship between prostate-specific antigen (PSA) level and positive imaging findings. Though limited randomized data are available, there appears to be increased sensitivity with the use of PSMA ligands compared with fluciclovine at low PSA values. Most studies have shown that only one-third to one-half of patients with detected lesions have lesions in the prostatic fossa alone. Management changes occur in nearly 50% of patients undergoing molecular imaging, and biochemical response in patients who undergo molecular PET-based RT planning appears to be statistically superior to the response in patients who undergo conventional imaging -based RT planning alone. High biochemical responses from molecular PET-based salvage RT, ranging from 45% to 94%, did not appear to come at the expense of increased genitourinary or gastrointestinal toxicity. The presence or absence of avid lesions appears to be a strong prognostic factor.

Conclusions: Molecular PET/CT imaging in the post-RP, pre-salvage RT setting often triggers management changes that result from detecting lesions in locations not typically included in consensus-driven postoperative RT fields. Ongoing trials will assess the benefit of PSMA PET in guiding salvage RT following RP and determine its impact on long-term outcomes.

Patient Summary: We reviewed and reported detection rates, detection patterns, and changes in management resulting from molecular positron emission tomography/computed tomography imaging in men with biochemically recurrent prostate cancer following radical prostatectomy. Prior to the receipt of salvage radiation therapy, molecular tracers targeting prostate-specific membrane antigen appear to be especially sensitive at identifying the place where prostate cancer has come back after surgery, which can help radiation oncologists better target the recurrent disease and potentially improve the rates of cure from prostate cancer in this setting. Future studies will determine whether these imaging tools will change cure rates and side effects, but early results are promising.
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http://dx.doi.org/10.1016/j.euo.2021.01.007DOI Listing
June 2021

Provider-Level Variation in Treatment Planning of Radiation Oncology Procedures in the United States.

JCO Oncol Pract 2021 Jan 8:OP2000441. Epub 2021 Jan 8.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA.

Purpose: Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them.

Methods: The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non-facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population.

Results: Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, = .02).

Conclusion: Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.
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http://dx.doi.org/10.1200/OP.20.00441DOI Listing
January 2021

A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER).

Eur Urol 2020 Dec 10. Epub 2020 Dec 10.

Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address:

Context: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.

Objective: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.

Evidence Acquisition: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.

Evidence Synthesis: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.

Conclusions: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.

Patient Summary: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
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http://dx.doi.org/10.1016/j.eururo.2020.11.010DOI Listing
December 2020

Non gastro-esophageal reflux disease related esophagitis: an overview with a histologic diagnostic approach.

Pathologica 2020 Sep;112(3):128-137

Anatomic Pathology, San Martino IRCCS Hospital, Genova, Italy.

Several pathological conditions, other than gastro-esophageal reflux disease and its complications, can affect the esophagus. While some of these can present with unspecific lesions (i.e. ulcers and epithelial damage) and require clinico-pathological correlation for diagnosis (i.e. drug-induced esophagitis and corrosive esophagitis) other conditions show distinctive histological lesions which enable the pathologist to reach the diagnosis (i.e. some specific infectious esophagites and Crohn's disease). In this context eosinophilic esophagitis is the condition which has been increasingly studied in the last two decades, while lymphocytic esophagitis, a relatively new entity, still represents an enigma. This overview will focus on and describe histologic lesions which allow pathologists to differentiate between these conditions.
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http://dx.doi.org/10.32074/1591-951X-156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931579PMC
September 2020

Missing the Near Miss: Recognizing Valuable Learning Opportunities in Radiation Oncology.

Pract Radiat Oncol 2021 May-Jun;11(3):e256-e262. Epub 2020 Sep 22.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.

Purpose: "Near miss" events are valuable low-cost learning opportunities in radiation oncology as they do not result in patient harm and are more pervasive than adverse events that do. Near misses vary depending on the presence of a latent error of behavior or process, and the presence of an enabling condition predisposing the patient to harm. These nuanced distinctions across near miss types can elicit different cognitive biases affecting the recognition of near misses as learning opportunities. We define near miss types in radiation oncology and explore the differential perceptions among radiation oncology staff.

Methods And Materials: Six event types were defined based on attributes of latent error and enabling conditions: "hit," "potential hit," "almost happened," "fortuitous catch," "could have happened," and "process-based catch." These events were illustrated with an example of a patient receiving pacemaker cardiac clearance before radiation treatment. A survey assessing (1) success versus failure of an event and (2) willingness to report the event was administered to a radiation oncology department using the pacemaker example. Mean scores for each near miss type were compared.

Results: Ninety-five staff members (74%) completed the survey. Perceived success scores and willing-to-report scores significantly differed by near miss type (P = .042 for success ratings; P < .0001 for willingness to report). "Could have happened" events were viewed as less successful and were more likely to be reported than "almost happened" events (P < .0001).

Conclusions: Cognitive biases appear to influence whether and how near miss types are recognized as report-worthy. Education of near miss types and engaging staff for quality improvement may improve recognition.
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http://dx.doi.org/10.1016/j.prro.2020.09.007DOI Listing
September 2020

Development and Validation of a Comprehensive Multivariate Dosimetric Model for Predicting Late Genitourinary Toxicity Following Prostate Cancer Stereotactic Body Radiotherapy.

Front Oncol 2020 20;10:786. Epub 2020 May 20.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, United States.

Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student -test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.
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http://dx.doi.org/10.3389/fonc.2020.00786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251156PMC
May 2020

Clinical Assessment of Prostate Displacement and Planning Target Volume Margins for Stereotactic Body Radiotherapy of Prostate Cancer.

Front Oncol 2020 16;10:539. Epub 2020 Apr 16.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, United States.

To assess the optimal planning target volume (PTV) margins for stereotactic body radiotherapy (SBRT) of prostate cancer based on inter- and intra-fractional prostate motion determined from daily image guidance. Two hundred and five patients who were enrolled on two prospective studies of SBRT (8 Gy × 5 fractions) for localized prostate cancer treated at a single institution between 2012 and 2017 had complete inter- and intra-fractional shift data available. All patients had scheduled kilovoltage planar imaging during SBRT with rigid registration to intraprostatic fiducials prior to each of four half-arcs delivered per fraction, as well as cone beam CT verification of anatomy prior to each fraction. Inter- and intra- fractional shift data were obtained to estimate the required PTV margins based on the classic van Herk formula. Inter- and intra-fractional motion were compared between patients with and without severe toxicities using the independent two-sample Wilcoxon test. The margins required to account for inter-fractional motion were estimated to be 0.99, 1.52, and 1.45 cm in lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. The margins required to account for intra-fractional motion were estimated to be 0.19, 0.27, and 0.31 cm in LR, SI and AP directions, respectively. Large intra-fractional shifts were mostly observed in the SI and AP directions, with 2.0 and 5.4% of patients experiencing average intra-fractional motion >3 mm in the SI and AP directions, respectively, compared with none experiencing mean shifts >3 mm in the LR direction. Six patients experienced grade 3 gastrointestinal or genitourinary toxicity. There were no significant differences in mean inter- or intra-fractional motion in any of the cardinal directions compared to patients without severe toxicity (inter-fractional = 0.46-0.99, intra-fractional = 0.10-0.84). The inter- and intra-fractional margins estimated from this study are in line with prior reported values. Intra-fractional prostate motion was generally small with larger margins required for the SI and AP directions, notably just slightly exceeding the commonly used 3 mm posterior PTV margin even with realignment between half-arcs. Development of severe toxicity was not significantly associated with the degree of inter- or intra-fractional motion.
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http://dx.doi.org/10.3389/fonc.2020.00539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177009PMC
April 2020

Rectal mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN): High grade evolution of a MANET?

Pathol Res Pract 2020 04 20;216(4):152869. Epub 2020 Feb 20.

Ospedale Policlinico San Martino IRCCS, Genova, Italy; Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Italy.

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http://dx.doi.org/10.1016/j.prp.2020.152869DOI Listing
April 2020

Lymph node number, surface area and lymph node ratio are important prognostic indicators in neoadjuvant chemoradiotherapy treated rectal cancer.

J Clin Pathol 2020 Mar 25;73(3):162-166. Epub 2019 Sep 25.

Department of Surgery, Ospedale Policlinico San Martino Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia, Genova, Italy.

Aims: Neoadjuvant chemoradiotherapy (neoCRT) is recommended for locally advanced rectal cancer (RC), however, this often makes lymph node (LN) search trying. The aim of this study was to evaluate, in a large retrospective, monocentric, series of post-neoCRT-RC patients, the importance of LN number, ratio and surface area in predicting metastases, overall survival (OS) and disease free survival (DFS).

Methods: 104 patients with RC underwent total mesorectal excision, after standard neoCRT. All resected specimens were examined according to a standardised sampling/histopathological protocol. The following data regarding LNs were collected: total numbers; number with metastases; LNratio (metastatic/total); maximum diameter; surface area.

Results: A statistically significant association was found between LN number and DFS (p=0.0473). Finding ≤9 or >20 LNs correlated with worse prognosis compared with 10-20 (p value=0.049). LNratio (>0.2) was strongly associated with shorter DFS (HR=13.36; p value <0.0001) and OS (HR=26.06; p value <0.0001). Poor outcome, for DFS (HR=2.17, p value =0.0416) and OS (HR=1.18, p value =0.0025), was associated with increasing LN surface area. LNratio was independently associated with DFS at multivariate analysis (p value <0.0001).

Conclusions: LN number, LNratio and LN surface area are important prognostic factors in neoCRT-RC and in particular finding ≤9 or >20 LNs is prognostically adverse.
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http://dx.doi.org/10.1136/jclinpath-2019-206139DOI Listing
March 2020

12-Lipoxygenase is a Critical Mediator of Type II Pneumocyte Senescence, Macrophage Polarization and Pulmonary Fibrosis after Irradiation.

Radiat Res 2019 08 2;192(4):367-379. Epub 2019 Aug 2.

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Radiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive complication of therapeutic irradiation of the thorax. It has been suggested that senescence of type II pneumocytes (AECIIs), an alveolar stem cell, plays a role in the development of RIPF through loss of replicative reserve and via senescent AECII-driven release of proinflammatory and profibrotic cytokines. Within this context, we hypothesized that arachidonate 12-lipoxygenase (12-LOX) is a critical mediator of AECII senescence and RIPF. Treatment of wild-type AECIIs with 12S-hydroxyeicosateraenoic acid (12S-HETE), a downstream product of 12-LOX, was sufficient to induce senescence in a NADPH oxidase 4 (NOX4)-dependent manner. Mice deficient in 12-LOX exhibited reduced AECII senescence, pulmonary collagen accumulation and accumulation of alternatively activated (M2) macrophages after thoracic irradiation (5 × 6 Gy) compared to wild-type mice. Conditioned media from irradiated or 12S-HETE-treated primary pneumocytes contained elevated levels of IL-4 and IL-13 compared to untreated pneumocytes. Primary macrophages treated with conditioned media from irradiated AECII demonstrated preferential M2 type polarization when AECIIs were derived from wild-type mice compared to 12-LOX-deficient mice. Together, these data identified 12-LOX as a critical component of RIPF and a therapeutic target for radiation-induced lung injury.
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http://dx.doi.org/10.1667/RR15356.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816027PMC
August 2019

Small Bowel Adenocarcinoma of Ileal Ureter 40 Years After Ureteral Reconstructive Surgery.

Urology 2019 Jul 19;129:e2-e3. Epub 2019 Apr 19.

Department of Health Sciences (DISSAL) - Radiology Section, University of Genoa, Genoa, Italy; Department of Emergency Radiology, Ospedale Policlinico San Martino, Genoa, Italy.

Malignant neoplasm arising from ileal ureter used for ureteral reconstructive surgery is an exceedingly rare event. Ureteroileoplasty was being performed since the beginning of the last century, but it was described more extensively in literature during the 1950s. Recurrent urinary infections, chronic renal failure, urolithiasis, anastomotic stricture, metabolic acidosis, and chronic dilation of the graft had been described as late complications of ureteroileoplasty. Herein, we describe history, imaging and pathologic findings of a small bowel adenocarcinoma arising from ileal ureter in a woman of 78-year-old, subjected to ureteroileoplasty about 40 years earlier.
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http://dx.doi.org/10.1016/j.urology.2019.04.011DOI Listing
July 2019

Assessment of Differences in Clinical Activity and Medicare Payments Among Female and Male Radiation Oncologists.

JAMA Netw Open 2019 03 1;2(3):e190932. Epub 2019 Mar 1.

Department of Radiation Oncology, University of California, Los Angeles.

Importance: Although physician sex is known to influence salary even after controlling for productivity, sex-based differences in clinical activity and reimbursement among radiation oncologists are poorly understood.

Objectives: To evaluate differences by sex in productivity, breadth of practice, and payments and to characterize Medicare reimbursement by sex among similarly productive groups of radiation oncologists.

Design, Setting, And Participants: A retrospective cohort study was conducted using the January 1 to December 31, 2016, Centers for Medicare & Medicaid Services Physician and Other Supplier Public Use File (POSPUF) to identify charge and payment information for individual radiation oncologists. Clinicians were part of a population-based sample of US radiation oncologists who bill Medicare in both non-facility-based (NFB) and facility-based (FB) practice settings. Analysis was conducted from June 5 to 25, 2018.

Main Outcomes And Measures: Outcome measurements included physician productivity (measured by number of Medicare charges), physician payments (reported as total Medicare payments as well as mean payments per charge submitted and per beneficiary treated), and physician breadth of practice (measured by number of unique Medicare billing codes) in NFB and FB settings.

Results: A total of 4393 radiation oncologists (1133 women and 3260 men) were included in the POSPUF in 2016. Compared with their male counterparts, female physicians in the NFB setting submitted a mean of 1051 fewer charges (95% CI, -1458 to -644; P < .001), collected a mean of $143 610 less in revenue (95% CI, -$185 528 to -$101 692; P < .001), and used a mean of 1.32 fewer unique billing codes (95% CI, -2.23 to -0.41; P = .004). Compared with their male counterparts, female radiation oncologists in the FB setting submitted a mean of 423 fewer charges (95% CI, -506 to -341; P < .001), collected a mean of $26 735 less in revenue (95% CI, -$31 910 to -$21 560; P < .001), and submitted a mean of 1.28 fewer unique billing codes (95% CI, -1.77 to -0.78; P < .001). Women represented 46 of the 397 most highly productive radiation oncologists in the FB setting (11.6%) and collected a mean of $33 026 less (95% CI, -$52 379 to -$13 673; P = .001) than men who were similarly productive. In the NFB setting, women represented 54 of the 326 most highly productive radiation oncologists (16.6%) and collected $345 944 (95% CI, -$522 663 to -$169 225; P < .001) less than similarly highly productive men. Women collected a mean of $8.49 less per charge (95% CI, -$14.13 to -$2.86; P = .003) than men in the NFB setting.

Conclusions And Relevance: This study suggests that female radiation oncologists submit fewer Medicare charges, are reimbursed less per charge they submit, and receive lower Medicare payments overall compared with male radiation oncologists. Even among similarly productive radiation oncologists, women in this study still collected less revenue than men. Further research is required to understand the sex-based barriers to economic advancement within radiation oncology.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.0932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583310PMC
March 2019

Abdominal Ectopic Thyroid Tissue: The Man From Istanbul.

Int J Surg Pathol 2019 Aug 14;27(5):553-555. Epub 2019 Mar 14.

1 University of Genoa, Genoa, Italy.

Thyroid ectopia is a rare finding below the diaphragm. It is characterized by normal thyroid parenchyma in unusual locations with preserved thyroid marker immunoreactivity. In this article, we present the first known case of thyroid tissue in the periappendiceal fat and discuss possible ethiopathogenic theories.
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http://dx.doi.org/10.1177/1066896919833784DOI Listing
August 2019

Agar pre-embedding of small skin biopsies: real-life benefits and challenges in high throughput pathology laboratories.

J Clin Pathol 2019 Jun 20;72(6):448-451. Epub 2019 Feb 20.

Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), Univeristy of Genoa, Genoa, Italy

Paraffin embedding of small, thin tissue samples requires specific expertise for optimal orientation before tissue sectioning. This study evaluates the real-life utility of the agar pre-embedding technique for small skin biopsies with regards to lengthening of work times, problems in orientation (re-embedding) and ancillary techniques (immunohistochemistry and in situ hybridisation) between two high work flow pathology laboratories, one of which routinely uses the agar pre-embedding technique and one which does not. The mean time required for pre-embedding in agar was 30.4 s, but time for paraffin embedding for agar pre-embedded samples was shorter than the traditional method (177 vs 296 s; p<0.005). The number of skin samples requiring re-embedding was significantly higher with the traditional embedding method (p<0.005). No problems in immunoreactivity were observed in all 1900 reactions performed with 17 different antibodies. Fluorescence in situ hybridisation analysis was optimised with a prolonged protease K incubation time (21 vs 18 min).
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http://dx.doi.org/10.1136/jclinpath-2018-205680DOI Listing
June 2019

Evaluation of Sex Distribution of Industry Payments Among Radiation Oncologists.

JAMA Netw Open 2019 01 4;2(1):e187377. Epub 2019 Jan 4.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California.

Importance: Industry relationships are an important measure of professional advancement; however, the association between physician sex and industry payments in radiation oncology has not been described.

Objective: To update the trends in the sex distribution of industry payments in radiation oncology.

Design, Setting, And Participants: This retrospective cross-sectional study was conducted between July 1, 2018, and August 31, 2018. It used the publicly available Centers for Medicare & Medicaid Services (CMS) Open Payments program and CMS Physician and Other Supplier Public Use File databases to obtain 2016 industry payment data for US radiation oncologists who reported receiving industry funding in that year (n = 3052). Total monetary value, number of payments, and median payment amounts were determined for each sex in the following categories: research, consulting, honoraria, industry grants, royalty or license, and services other than consulting.

Main Outcomes And Measures: Industry payment amounts among 3052 radiation oncologists who reported receiving payments in 2016; association of median payment with the types of payment by sex.

Results: Of the total 4483 radiation oncologists who practiced in 2016, 1164 (25.9%) were female and 3319 (74.0%) were male. Industry payments were distributed among 3052 radiation oncologists (68.1%), of whom 715 (23.4%) were female and 2337 (76.6%) were male. The proportion of female radiation oncologists who received at least 1 industry payment was 61.4% (715 of 1164), whereas the proportion of their male counterparts was 70.4% (2337 of 3319). Across all payment types, female radiation oncologists received a smaller percentage of total industry funding than the percentage of female physicians represented in each category. The median payment value was smaller for female radiation oncologists in consulting (-$1000; 95% CI, -$1966.67 to $100.63; P = .005) and honoraria (-$500; 95% CI, -$1071.43 to $0; P = .007). This trend was also observed in research payments, but was not statistically significant (-$135.02; 95% CI, -$476.93 to $6.88; P = .08). Of the $1 347 509 royalty or license payments made to 72 physicians, none was for female radiation oncologists.

Conclusions And Relevance: Distribution of industry payments appears to show sex disparity in industry relationships among radiation oncologists; this observation warrants further investigation to determine the underlying reasons and provide avenues for increased parity.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.7377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484553PMC
January 2019

Sentinel lymph node biopsy in porocarcinoma: A case reports.

Int J Surg Case Rep 2018 31;53:196-199. Epub 2018 Oct 31.

Department of Surgery, Chirurgia I- Ospedale Policlinico San Martino Genoa, Italy.

Introduction: Eccrine porocarcinoma (EPC) is a slow-growing carcinoma arising from the eccrine sweat glands. Based on its clinical presentation it can be confused with malignant and benign skin lesions, both. Histological examination is essential to formulate a correct diagnosis. Surgical excision with clear margins is the standard therapeutic approach while the role of sentinel lymph node biopsy (SNLB) remains controversial.

Case Presentation: The Authors report two cases of EPC of the lower limbs occurred in two women. Patients were treated by wide surgical excision of the lesion and SNLB. 6 months follow-up was disease free for both patients.

Conclusion: Although a rare cutaneous tumor, EPC has to be taken into account in the differential diagnosis of malignant skin lesions because of its possible loco-regional aggressiveness and related morbidity. Among the available treatment options, surgical excision is considered the standard approach whereas the role of SNLB is controversial although the Authors discuss a possible usefulness for staging and diagnosis.
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http://dx.doi.org/10.1016/j.ijscr.2018.10.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226587PMC
October 2018

Organ-Specific Toxicities Due to Radiation Therapy in Cancer Patients With or Without HIV Infection: A Systematic Review of the Literature.

Front Oncol 2018 30;8:276. Epub 2018 Jul 30.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States.

To synthesize published literature on the association between human immunodeficiency virus (HIV) infection and radiation therapy (RT)-related toxicities. Two electronic databases, MEDLINE and Embase, were searched to identify studies published before November 2016 comparing RT-related toxicities between HIV-infected and HIV-uninfected patients receiving RT or chemoradiation therapy (CRT) for cancer. A qualitative synthesis of included articles and organ-specific toxicities was then performed. Of the 21 studies included in this review, 15 reported on anal cancer treatment, three on cervical cancer, two on Kaposi sarcoma, and one on prostate cancer. Reports in the pre-antiretroviral therapy (ART) or early ART era tended to identify increased morbidity and mortality with HIV infection. However, modern series incorporating more concurrent chemotherapy, conformal RT techniques, and ART administration result in fewer studies reporting toxicity differences in patients treated for anal and cervical cancers. When statistically significant, HIV-infected patients had higher rates of gastrointestinal toxicity with anal cancer CRT (up to 50%) and higher rates of hematologic toxicity with cervical cancer CRT (up to 31%). Of the 17 studies reporting treatment outcomes, nine suggest HIV-infected patients may have reduced local control and/or survival rates. Overall, RT is likely similarly tolerated between HIV-infected and HIV-uninfected patients, especially with modern RT techniques. HIV-infected patients should continue to receive established standard of care RT and CRT dosing.
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http://dx.doi.org/10.3389/fonc.2018.00276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077254PMC
July 2018

Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low dose rate brachytherapy.

Diagn Interv Radiol 2018 Jan-Feb;24(1):46-53

Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Maryland, USA.

Purpose: Prostate multiparametric magnetic resonance imaging (mpMRI) has utility in detecting post-radiotherapy local recurrence. We conducted a multireader study to evaluate the diagnostic performance of mpMRI for local recurrence after low dose rate (LDR) brachytherapy.

Methods: A total of 19 patients with biochemical recurrence after LDR brachytherapy underwent 3T endorectal coil mpMRI with T2-weighted imaging, dynamic contrast-enhanced imaging (DCE) and diffusion-weighted imaging (DWI) with pathologic confirmation. Prospective reads by an experienced prostate radiologist were compared with reads from 4 radiologists of varying experience. Readers identified suspicious lesions and rated each MRI detection parameter. MRI-detected lesions were considered true-positive with ipsilateral pathologic confirmation. Inferences for sensitivity, specificity, positive predictive value (PPV), kappa, and index of specific agreement were made with the use of bootstrap resampling.

Results: Pathologically confirmed recurrence was found in 15 of 19 patients. True positive recurrences identified by mpMRI were frequently located in the transition zone (46.7%) and seminal vesicles (30%). On patient-based analysis, average sensitivity of mpMRI was 88% (standard error [SE], 3.5%). For highly suspicious lesions, specificity of mpMRI was 75% (SE, 16.5%). On lesion-based analysis, the average PPV was 62% (SE, 6.7%) for all lesions and 78.7% (SE, 10.3%) for highly suspicious lesions. The average PPV for lesions invading the seminal vesicles was 88.8% (n=13). The average PPV was 66.6% (SE, 5.8%) for lesions identified with T2-weighted imaging, 64.9% (SE, 7.3%) for DCE, and 70% (SE, 7.3%) for DWI.

Conclusion: This series provides evidence that mpMRI after LDR brachytherapy is feasible with a high patient-based cancer detection rate. Radiologists of varying experience demonstrated moderate agreement in detecting recurrence.
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http://dx.doi.org/10.5152/dir.2018.17285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765929PMC
August 2018

Mithramycin A Enhances Tumor Sensitivity to Mitotic Catastrophe Resulting From DNA Damage.

Int J Radiat Oncol Biol Phys 2018 02 12;100(2):344-352. Epub 2017 Oct 12.

Radiation Oncology Branch, National Institutes of Health, Bethesda, Maryland. Electronic address:

Purpose: Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response.

Methods And Materials: Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology. Gene expression was evaluated using polymerase chain reaction arrays. In vivo tumor growth delay was used to evaluate the effects of MTA on radiosensitivity.

Results: Targeting of SP1 with small interfering RNA or MTA sensitized A549 and UM-UC-3 to irradiation, with no effect on the BJ radiation response. MTA did not alter γH2AX foci formation after irradiation in tumor cells but did enhance mitotic catastrophe. Treatment with MTA suppressed transcription of genes involved in cell death. MTA administration to mice bearing A549 and UM-UC-3 xenografts enhanced radiation-induced tumor growth delay.

Conclusions: These results support SP1 as a target for radiation sensitization and confirm MTA as a radiation sensitizer in human tumor models.
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http://dx.doi.org/10.1016/j.ijrobp.2017.09.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777897PMC
February 2018

Patterns of Treatment and Outcomes for Definitive Therapy of Early Stage Non-Small Cell Lung Cancer.

Ann Thorac Surg 2017 Dec 26;104(6):1881-1888. Epub 2017 Oct 26.

Simon Cancer Center at Indiana University, Indianapolis, Indiana.

Background: Definitive surgical and radiation therapy (RT) treatments are evolving rapidly for stage I non-small cell lung cancer (NSCLC). We hypothesized that utilization of definitive therapies increased between 2000 and 2010 and that survival improved for stage I NSCLC patients over the same time period. Secondary objectives were determining trends in patterns of care and predictors of utilization.

Methods: Population-based, observational, comparative effectiveness study used Surveillance, Epidemiology, and End Results-18 data from 2000 to 2010. The main outcome measure was 2-year risk of death for stage I NSCLC.

Results: Between 2000 and 2010, 40,589 patients (62%) underwent surgery, 10,048 (15%) received RT, 2,130 (3%) received both surgery and RT, and 11,537 (18%) received neither surgery nor RT. Annually, the odds of receiving either definitive RT or undergoing surgery increased relative to the odds of receiving no treatment (odds ratio [OR] radiation 1.04, 95% confidence interval [CI]: 1.03 to 1.05; OR surgery 1.05, 95% CI: 1.04 to 1.05). Among surgical patients, the proportion of sublobar resections steadily increased from 12.9% to 17.9%. For all patients, the 2-year risk of death decreased by 3.5% each year (hazard ratio [HR] 0.965, 95% CI: 0.962 to 0.969), driven primarily by improved survival for surgical (annualized HR 0.959, 95% CI: 0.954 to 0.964) and RT (annualized HR 0.942, 95% CI: 0.935 to 0.949) patients.

Conclusions: Between 2000 and 2010, stage I NSCLC patients were more likely to receive definitive treatment with either surgery or RT, leading to a decline in the number of untreated patients. Survival also improved substantially for stage I NSCLC patients, with the largest survival improvements observed in patients undergoing definitive RT.
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http://dx.doi.org/10.1016/j.athoracsur.2017.06.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889065PMC
December 2017

Erratum to: KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

Endocrine 2017 09;57(3):503

Pathology Unit, Department of Surgical Science and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi, 10, Genoa, 16132, Italy.

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http://dx.doi.org/10.1007/s12020-017-1389-zDOI Listing
September 2017

KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

Endocrine 2017 Sep 19;57(3):494-502. Epub 2017 Jul 19.

Pathology Unit, Department of Surgical Science and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi, 10, Genoa, 16132, Italy.

Purpose: Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens.

Method: To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy.

Results: Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%.

Conclusions: By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm, and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not <12 mm should be performed; using 18G needles, this corresponds to a minimum total length of 15 mm.
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http://dx.doi.org/10.1007/s12020-017-1364-8DOI Listing
September 2017

Hepatoid adenocarcinoma of the lung metastasizing to the tonsil.

Mol Clin Oncol 2017 May 10;6(5):705-707. Epub 2017 Apr 10.

Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1906, USA.

Hepatoid adenocarcinoma (HAC) is a rare tumor that typically originates in gastrointestinal tissue, such as the stomach, but can also occasionally originate in the lung. The majority of HACs express α-fetoprotein (AFP) on tumor cells, and serum AFP can be used as a marker of response to treatment or disease progression. HAC has a poor prognosis, although early diagnosis and aggressive treatment can result in long-term survival. To the best of our knowledge, this is the first reported case of HAC metastasizing to the tonsil. Irradiation using intensity-modulated radiation therapy (IMRT) to 30 Gray (Gy) achieved a significant, and durable tumor response. IMRT can be considered for local control of HAC at other metastatic sites of disease.
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http://dx.doi.org/10.3892/mco.2017.1215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431682PMC
May 2017

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations.

Int J Radiat Oncol Biol Phys 2017 04 18;97(5):947-951. Epub 2016 Dec 18.

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Purpose: Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations.

Methods And Materials: All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network risk groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated.

Results: From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients).

Conclusions: In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.
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http://dx.doi.org/10.1016/j.ijrobp.2016.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364814PMC
April 2017

Hypofractionated whole breast radiotherapy in breast conservation for early-stage breast cancer: a systematic review and meta-analysis of randomized trials.

Breast Cancer Res Treat 2017 04 3;162(3):409-417. Epub 2017 Feb 3.

The Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

Purpose: Breast conservation therapy (BCT) for early-stage breast cancer involves lumpectomy followed by whole breast radiotherapy, which can involve either standard fractionation (SRT) or accelerated fractionation (ART). This systematic review and meta-analysis was performed to determine whether any benefit exists for ART or SRT.

Materials And Methods: We searched MEDLINE (1966-2014), all seven databases of the Cochrane Library (1968-2014), EMBASE (1974-2014), clinicaltrials.gov, ISRCTN, WHO ICTRP, and meeting abstracts in the Web of Science Core Collection (1900-2014). RCTs comparing SRT to ART among women undergoing BCT with stage T1-T2 and/or N1 breast cancer or carcinoma in situ were included. Follow-up was 30 days for acute toxicity, or three years for disease control and late toxicity.

Results: 13 trials with 8189 participants were included. No differences were observed in local failure (n = 7 trials; RR 0.97; 95% CI 0.78-1.19, I  = 0%), locoregional failure, (n = 8 trials; RR 0.86; 95% CI 0.63-1.16, I  = 0%), or survival (n = 4 trials; RR 1.00; 95% CI 0.85-1.17, I  = 0%). ART was associated with significantly less acute toxicity (n = 5 trials; RR 0.36; 95% CI 0.21-0.62, I  = 20%), but no difference in late cosmesis (RR 0.95; 95% CI 0.81-1.12, I  = 54%).

Conclusions: ART use does not reduce disease control or worsen long-term cosmetic outcome, and may decrease the risk of acute radiation toxicity as compared to SRT.
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http://dx.doi.org/10.1007/s10549-017-4118-7DOI Listing
April 2017
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