Improved survival for extremity soft tissue sarcoma treated in high‐volume facilities

Journal of Surgical Oncology, EarlyView.


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Chernobyl-related thyroid cancer

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Proton therapy for central nervous system tumors in children

Pediatric Blood &Cancer, EarlyView.


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Malignant tumors misdiagnosed as benign vascular anomalies

Pediatric Blood &Cancer, EarlyView.


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Proton therapy for central nervous system tumors in children

Pediatric Blood &Cancer, EarlyView.


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Malignant tumors misdiagnosed as benign vascular anomalies

Pediatric Blood &Cancer, EarlyView.


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Reducing the risk of post-surgical cancer recurrence: a perioperative anti-inflammatory anti-stress approach

Future Oncology, Ahead of Print.


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Management of oncological patients in the digital era: anatomic pathology and nuclear medicine teamwork

Future Oncology, Ahead of Print.


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Treatment of venous stenosis in oncologic patients

Future Oncology, Ahead of Print.


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Reducing the risk of post-surgical cancer recurrence: a perioperative anti-inflammatory anti-stress approach

Future Oncology, Ahead of Print.


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Management of oncological patients in the digital era: anatomic pathology and nuclear medicine teamwork

Future Oncology, Ahead of Print.


https://ift.tt/2HeOzzK

Treatment of venous stenosis in oncologic patients

Future Oncology, Ahead of Print.


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BRAF gene copy number and mutant allele frequency correlate with time to progression in metastatic melanoma patients treated with MAPK inhibitors.

Metastatic melanoma is characterized by complex genomic alterations including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pre-treatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy and we analyzed the association with progression free survival. We found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF mutant/wild-type allele ratio, while 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status vs. those with BRAF gains (HR = 2.86; 95% CI 1.29-6.35; p = 0.01) and in patients with low percentage vs. those with a balanced BRAF mutant allele percentage (HR = 4.54, 95% CI 1.33-15.53; p = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors.

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APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency

APTO-253 is a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interactions that can guide combination studies. The cellular pharmacology of APTO-253 was analyzed in Raji lymphoma cells and a subline selected for resistance (Raji/253R). Using LC/MS/ESI analysis, APTO-253 was found to convert intracellularly to a complex containing one molecule of iron and three molecules of APTO-253 [Fe(253)3]. The intracellular content of Fe(253)3 exceeded that of the native drug by ~18-fold, and Fe(253)3 appears to be the most active form. Treatment of cells with APTO-253 caused DNA damage, which led us to ask if cells deficient in homologous recombination (i.e., loss of BRCA1/2 function) were hypersensitive to this drug. It was found that loss of either BRCA1 or BRCA2 function in multiple isogenic paired cell lines resulted in hypersensitivity to APTO-253 of a magnitude similar to the effects of PARP inhibitors, olaparib. Raji cells selected for 16-fold acquired resistance had 16-fold reduced accumulation of Fe(253)3. RNA-seq analysis revealed that over-expression of the ABCG2 drug efflux pump is a key mechanism of resistance. ABCG2 overexpressed HEK-293 cells were resistant to APTO-253 and inhibition of ABCG2 reversed resistance to APTO-253 in Raji/253R. APTO-253 joins the limited repertoire of drugs which can exploit defects in homologous recombination and is of particular interest because it does not produce myelosuppression.

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APTO-253 stabilizes G-quadruplex DNA, inhibits MYC expression and induces DNA damage in acute myeloid leukemia cells

APTO-253 is a Phase 1 clinical stage small molecule that selectively induces CDKN1A (p21), promotes G0/G1 cell cycle arrest and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration-dependent and time-dependent reduction in MYC mRNA expression and protein levels. Gene ontogeny and structural informatic analyses suggested a mechanism involving G-quadruplex (G4) stabilization. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253)3]. FRET assays demonstrated that both monomeric APTO-253 and Fe(253)3 stabilize G4 structures from telomeres, MYC and KIT promoters but do not bind to non-G4 double stranded DNA. Although APTO-253 exerts a host of mechanistic sequelae, the effect of APTO-253 on MYC expression and its downstream target genes, on cell cycle arrest, DNA damage, and stress responses can be explained by the action of Fe(253)3 and APTO-253 on G-quadruplex DNA motifs.

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BRAF gene copy number and mutant allele frequency correlate with time to progression in metastatic melanoma patients treated with MAPK inhibitors.

Metastatic melanoma is characterized by complex genomic alterations including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pre-treatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy and we analyzed the association with progression free survival. We found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF mutant/wild-type allele ratio, while 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status vs. those with BRAF gains (HR = 2.86; 95% CI 1.29-6.35; p = 0.01) and in patients with low percentage vs. those with a balanced BRAF mutant allele percentage (HR = 4.54, 95% CI 1.33-15.53; p = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors.

https://ift.tt/2H1J4Xi

APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency

APTO-253 is a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interactions that can guide combination studies. The cellular pharmacology of APTO-253 was analyzed in Raji lymphoma cells and a subline selected for resistance (Raji/253R). Using LC/MS/ESI analysis, APTO-253 was found to convert intracellularly to a complex containing one molecule of iron and three molecules of APTO-253 [Fe(253)3]. The intracellular content of Fe(253)3 exceeded that of the native drug by ~18-fold, and Fe(253)3 appears to be the most active form. Treatment of cells with APTO-253 caused DNA damage, which led us to ask if cells deficient in homologous recombination (i.e., loss of BRCA1/2 function) were hypersensitive to this drug. It was found that loss of either BRCA1 or BRCA2 function in multiple isogenic paired cell lines resulted in hypersensitivity to APTO-253 of a magnitude similar to the effects of PARP inhibitors, olaparib. Raji cells selected for 16-fold acquired resistance had 16-fold reduced accumulation of Fe(253)3. RNA-seq analysis revealed that over-expression of the ABCG2 drug efflux pump is a key mechanism of resistance. ABCG2 overexpressed HEK-293 cells were resistant to APTO-253 and inhibition of ABCG2 reversed resistance to APTO-253 in Raji/253R. APTO-253 joins the limited repertoire of drugs which can exploit defects in homologous recombination and is of particular interest because it does not produce myelosuppression.

https://ift.tt/2IvS1p9

APTO-253 stabilizes G-quadruplex DNA, inhibits MYC expression and induces DNA damage in acute myeloid leukemia cells

APTO-253 is a Phase 1 clinical stage small molecule that selectively induces CDKN1A (p21), promotes G0/G1 cell cycle arrest and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration-dependent and time-dependent reduction in MYC mRNA expression and protein levels. Gene ontogeny and structural informatic analyses suggested a mechanism involving G-quadruplex (G4) stabilization. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253)3]. FRET assays demonstrated that both monomeric APTO-253 and Fe(253)3 stabilize G4 structures from telomeres, MYC and KIT promoters but do not bind to non-G4 double stranded DNA. Although APTO-253 exerts a host of mechanistic sequelae, the effect of APTO-253 on MYC expression and its downstream target genes, on cell cycle arrest, DNA damage, and stress responses can be explained by the action of Fe(253)3 and APTO-253 on G-quadruplex DNA motifs.

https://ift.tt/2H45V4L

The Structure of GATOR1-Rag GTPases Reveal Modes of Regulation [Research Watch]

A Rag GTPases–DEPDC5 inhibitory interaction mode suppresses GATOR1 GAP activity.

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Immune Checkpoint Blockade Is Active in Melanoma Brain Metastases [Research Watch]

Treatment with nivolumab alone or nivolumab plus ipilimumab achieves intracranial responses.

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Trastuzumab Extends Progression-Free Survival in HER2/neu+ Uterine Tumors [Research Watch]

Adding trastuzumab to carboplatin–paclitaxel is well tolerated in patients with uterine serous carcinoma.

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Blocking MICA/MICB Shedding Reactivates Antitumor Immunity [Research Watch]

Inhibition of protease-driven MICA and MICB shedding enhances NK cell–mediated tumor immunity.

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Ibrutinib plus Venetoclax May Be Effective in Mantle-Cell Lymphoma [Research Watch]

Ibrutinib plus venetoclax is superior to monotherapy in patients with mantle-cell lymphoma.

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New Visions and Current Evidence for Safety in Anesthesia

No abstract available

https://ift.tt/2qbiaCO

American Society for Enhanced Recovery: Advancing Enhanced Recovery and Perioperative Medicine

As the population ages, the increasing surgical volume and complexity of care are expected to place additional care delivery burdens in the perioperative setting. In this age of integrated multidisciplinary care of the surgical patients, there is increasing recognition that an evidence-based perioperative pathway is associated with the optimal outcomes. These pathways, collectively referred to as Enhanced Recovery Pathways, have resulted in shortened length of hospital stay, reduced complications, and variance in outcomes, as well as earlier return to baseline activities. The American Society for Enhanced Recovery (ASER) is a multispecialty, nonprofit international organization, dedicated to the practice of enhanced recovery in perioperative patients through education and research. Perioperative Quality Initiatives were formed whose intent is to organize a series of consensus conferences on topics of interest related to perioperative medicine. The journal affiliation between American Society for Enhanced Recovery and Anesthesia& Analgesia will enable these evidence-based practices to be disseminated widely and swiftly to the practicing perioperative health care professionals so they can be adopted to improve the quality of perioperative surgical care. Accepted for publication March 12, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Tong J. Gan, MD, MBA, MHS, FRCA, Department of Anesthesiology, Stony Brook University, HSC Level 4, Rm 060, Stony Brook, NY 11794. Address e-mail to tong.gan@stonybrookmedicine.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2uRHhj3

Dezocine Alleviates Morphine-Induced Dependence in Rats

BACKGROUND: Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models. METHODS: Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein–coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets. RESULTS: The mean withdrawal score was reduced in rats treated with 1.25 mg·kg−1 dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35–9.25; P

https://ift.tt/2JsGb02

Case Studies in Adult Intensive Care Medicine

No abstract available

https://ift.tt/2uQZFs2

Lack of Evidence for Ceiling Effect for Buprenorphine Analgesia in Humans

No abstract available

https://ift.tt/2JsG6JM

Potential Benefits of Sodium-Glucose Cotransporter-2 Inhibitors in the Perioperative Period

No abstract available

https://ift.tt/2ErU6zY

Diagnostic Accuracy of Point-of-Care Gastric Ultrasound

BACKGROUND: Pulmonary aspiration of gastric contents is associated with significant perioperative morbidity and mortality. Previous studies have investigated the validity, reliability, and possible clinical impact of gastric ultrasound for the assessment of gastric content at the bedside. In the present study, we examined the accuracy (evaluated as sensitivity, specificity, and likelihood ratios) of point-of-care gastric ultrasound to detect a "full stomach" in a simulated scenario of clinical equipoise. METHODS: After a minimum fasting period of 8 hours, 40 healthy volunteers were randomized in a 1:1 ratio to either remain fasted or ingest a standardized quantity of clear fluid or solid. Each subject was randomized twice on 2 independent study sessions at least 24 hours apart. A gastric ultrasound examination was performed by a blinded sonographer following a standardized scanning protocol. Using a combination of qualitative and quantitative findings, the result was summarized in a dichotomous manner as positive (any solid or >1.5 mL/kg of clear fluid) or negative (no solid and ≤1.5 mL/kg of clear fluid) for full stomach. RESULTS: Data from 80 study sessions were analyzed. In this simulated clinical scenario with a pretest probability of 50%, point-of-care gastric ultrasound had a sensitivity of 1.0 (95% confidence interval [CI], 0.925–1.0), a specificity of 0.975 (95% CI, 0.95–1.0), a positive likelihood ratio of 40.0 (95% CI, 10.33–∞), a negative likelihood ratio of 0 (95% CI, 0–0.072), a positive predictive value of 0.976 (95% CI, 0.878–1.0), and a negative predictive value of 1.0 (95% CI, 0.92–1.0). CONCLUSIONS: Our results suggest that bedside gastric ultrasound is highly sensitive and specific to detect or rule out a full stomach in clinical scenarios in which the presence of gastric content is uncertain. Accepted for publication February 27, 2018. Funding: This study was supported by a peer-reviewed grant from Physician Services Incorporated, Ontario, Canada. Conflicts of Interest: See Disclosures at the end of the article. Trial Registry Number: Registration ID: NCT02588495. Reprints will not be available from the authors. Address correspondence to Anahi Perlas, MD, FRCPC, Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Department of Anesthesia, University of Toronto, 399 Bathurst St, McLaughlin Pavilion 2–405, Toronto, ON M5T 2S8, Canada. Address e-mail to anahi.perlas@uhn.ca. © 2018 International Anesthesia Research Society

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In Response

No abstract available

https://ift.tt/2uRBfPd

Reduced Ketobemidone Usage in Quadratus Lumborum Block Patients After Cesarean Delivery: Clinical Pharmacology Views

No abstract available

https://ift.tt/2JrNiWM

Profound Intraoperative Hypotension Associated With Transfusion via the Belmont Fluid Management System

This retrospective observational case series conducted at 2 large academic centers over a 4-year period consists of 15 cases of profound hypotension in surgical patients immediately after initiation of the Belmont Fluid Management System for rapid transfusion of blood products. Halting the infusion and administering vasoactive agents led to resolution of hypotension. Repeat transfusion with the Belmont system resulted in repeat hypotension unless counteracted with vasopressors. No etiology was elucidated. This represents the largest documented association of acute hypotensive transfusion reaction with any rapid infusion system in surgical patients. Accepted for publication February 1, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Joanna Miller, MD, Mount Sinai Hospital, 1 Gustave Levy Pl, New York, NY 10129. Address e-mail to joanna.miller@mountsinai.org. © 2018 International Anesthesia Research Society

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In Response

No abstract available

https://ift.tt/2q9JFgi

Comparison of Intraoperative Sedation With Dexmedetomidine Versus Propofol on Acute Postoperative Pain in Total Knee Arthroplasty Under Spinal Anesthesia: A Randomized Trial

BACKGROUND: In patients undergoing total knee arthroplasty under spinal anesthesia, we compared the postoperative analgesic effect of intraoperative sedation with dexmedetomidine versus propofol. We hypothesized that sedation with dexmedetomidine would result in lower postoperative opioid analgesic consumption than with propofol. METHODS: Forty-eight patients were enrolled and randomly assigned to either a dexmedetomidine group (n = 24), which received a loading dose of 1 μg/kg dexmedetomidine over 10 minutes, followed by a continuous infusion of 0.1–0.5 μg·kg−1·hour−1, or a propofol group (n = 24), which received a continuous infusion of propofol via a target-controlled infusion to maintain the effect-site concentration within a range of 0.5–2.0 μg/mL. The drug infusion rate was determined according to the sedation level, targeting a modified observer's assessment of alertness/sedation score of 3 or 4. The cumulative amounts of fentanyl administered via intravenous patient-controlled analgesia were recorded at 24 and 48 hours postoperatively (primary outcome). The postoperative numerical rating scale for pain was assessed at 6, 12, 24, and 48 hours (secondary outcome). The postoperative use of additional rescue analgesic (ketoprofen) and antiemetic drugs was also compared between the 2 groups at 24 and 48 hours. RESULTS: Dexmedetomidine significantly reduced postoperative fentanyl consumption (median [interquartile range]) during 0–24 hours (45 [30–71] vs 150 [49–248] μg, P = .004; median difference = −105 μg [99.98% CI, 210–7.5]), 24–48 hours (90 [45–143] vs 188 [75–266] μg, P = .005; median difference = −98 μg [99.98% CI, 195–45]), and 0–48 hours (135 [68–195] vs 360 [146–480] μg, P = .003; median difference = −225 μg [99.98% CI, 405–7.5]). The numerical rating scale (median [interquartile range]) was lower at 6 hours (1 [0–2] vs 2 [1–3], P = .003), 12 hours (1 [1–2] vs 3 [2–3], P

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Flupirtine, an Effective Analgesic, but Hepatotoxicity Should Limit Its Use

No abstract available

https://ift.tt/2qbEwnS

Using Synthetic CT for Partial Brain Radiation Therapy: Impact on Image Guidance

Publication date: Available online 6 April 2018
Source:Practical Radiation Oncology
Author(s): Eric D. Morris, Ryan G. Price, Joshua Kim, Lonni Schultz, M. Salim Siddiqui, Indrin Chetty, Carri Glide-Hurst
PurposeRecent advancements in synthetic computed tomography (synCTs) from MRI data have made MR-only treatment planning feasible in brain, although synCT performance for IGRT is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT.MethodsTen brain cancer patients (12 lesions, 7 post-surgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and FLAIR datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index (OI), Dice similarity coefficient (DSC), and Jaccard index (JI). Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2D-2D rigid registrations using normalized mutual information (NMI). Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3D vector difference. 1490 rigid registrations were assessed.ResultsDRR agreements in anterior–posterior and lateral views for OI, DSC, and JI were>0.95. NMI results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (p<0.05). The population average absolute shifts were 0.77±0.58mm and 0.76±0.59mm for CT and synCT, respectively for all axes/quadrants. 3D vectors were<2mm in 77.7±10.8% and 76.5±7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in post-surgical cases (vector displacements >2mm in affected quadrants).ConclusionDRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in post-surgical settings.



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Using Synthetic CT for Partial Brain Radiation Therapy: Impact on Image Guidance

Publication date: Available online 6 April 2018
Source:Practical Radiation Oncology
Author(s): Eric D. Morris, Ryan G. Price, Joshua Kim, Lonni Schultz, M. Salim Siddiqui, Indrin Chetty, Carri Glide-Hurst
PurposeRecent advancements in synthetic computed tomography (synCTs) from MRI data have made MR-only treatment planning feasible in brain, although synCT performance for IGRT is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT.MethodsTen brain cancer patients (12 lesions, 7 post-surgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and FLAIR datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index (OI), Dice similarity coefficient (DSC), and Jaccard index (JI). Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2D-2D rigid registrations using normalized mutual information (NMI). Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3D vector difference. 1490 rigid registrations were assessed.ResultsDRR agreements in anterior–posterior and lateral views for OI, DSC, and JI were>0.95. NMI results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (p<0.05). The population average absolute shifts were 0.77±0.58mm and 0.76±0.59mm for CT and synCT, respectively for all axes/quadrants. 3D vectors were<2mm in 77.7±10.8% and 76.5±7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in post-surgical cases (vector displacements >2mm in affected quadrants).ConclusionDRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in post-surgical settings.



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Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Objective: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. Methods: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. Results: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. Conclusions: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes. V.A. and A.K. contributed equally. The authors declare no conflicts of interest. Reprints: Linus Chuang, MD, Division of Gynecologic Oncology, Icahn School of Medicine at Mount Sinai, 1176 Fifth Avenue, 1st Floor, New York, NY 10029. E-mail: linus.chuang@mountsinai.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Introduction: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. Methods: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. Results: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P

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Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Objective: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. Methods: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. Results: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. Conclusions: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes. V.A. and A.K. contributed equally. The authors declare no conflicts of interest. Reprints: Linus Chuang, MD, Division of Gynecologic Oncology, Icahn School of Medicine at Mount Sinai, 1176 Fifth Avenue, 1st Floor, New York, NY 10029. E-mail: linus.chuang@mountsinai.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Introduction: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. Methods: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. Results: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P

https://ift.tt/2qaSVQX

A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women

International Journal of Cancer, EarlyView.


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Is the incidence of advanced‐stage breast cancer affected by whether women attend a steady‐state screening program?

International Journal of Cancer, EarlyView.


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Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies

International Journal of Cancer, EarlyView.


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A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women

International Journal of Cancer, EarlyView.


https://ift.tt/2uS1Ewu

Is the incidence of advanced‐stage breast cancer affected by whether women attend a steady‐state screening program?

International Journal of Cancer, EarlyView.


https://ift.tt/2JnEst4

Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies

International Journal of Cancer, EarlyView.


https://ift.tt/2EqKa9O

Down‐regulation of POTEG predicts poor prognosis in esophageal squamous cell carcinoma patients

Molecular Carcinogenesis, EarlyView.


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Aberrant methylation‐mediated downregulation of long noncoding RNA C5orf66‐AS1 promotes the development of gastric cardia adenocarcinoma

Molecular Carcinogenesis, EarlyView.


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Role of radiation therapy in primary breast diffuse large B‐cell lymphoma in the Rituximab era: a SEER database analysis

Cancer Medicine, EarlyView.


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Down‐regulation of POTEG predicts poor prognosis in esophageal squamous cell carcinoma patients

Molecular Carcinogenesis, EarlyView.


https://ift.tt/2HgIdQy

Aberrant methylation‐mediated downregulation of long noncoding RNA C5orf66‐AS1 promotes the development of gastric cardia adenocarcinoma

Molecular Carcinogenesis, EarlyView.


https://ift.tt/2EqFIb6

Role of radiation therapy in primary breast diffuse large B‐cell lymphoma in the Rituximab era: a SEER database analysis

Cancer Medicine, EarlyView.


https://ift.tt/2H3D0xJ

A contemporary analysis of radiotherapy effect in surgically treated retroperitoneal sarcoma

Contemporary data regarding the benefit of radiotherapy in surgically treated retroperitoneal sarcoma are scarce. The aim of the study was to evaluate the effect of radiotherapy on cancer specific mortality in surgically treated patients according to tumor size, histological subtype and grade.

https://ift.tt/2GYPczF

Physician assessed and patient reported lower limb edema after definitive radio(chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: A report from the EMBRACE study

To evaluate the pattern of manifestation and risk factors for lower limb edema (LLE) within the prospective, observational, multi-center EMBRACE study on radiochemotherapy and MRI-guided brachytherapy in locally advanced cervical cancer (LACC).

https://ift.tt/2GHuTDE

Role of adjuvant external beam radiotherapy and chemotherapy in one versus two or more node-positive vulvar cancer: A National Cancer Database study

Inguinal lymph node involvement is considered the most important prognostic risk factor for survival in vulvar cancer. However, controversy exists concerning the optimal adjuvant therapy for node-positive disease. This study sought to identify the optimal adjuvant therapy for each subset of women with node-positive disease.

https://ift.tt/2H4BLhQ

LncRNA PlncRNA-1 overexpression inhibits the growth of breast cancer by upregulating TGF-β1 and downregulating PHGDH

Abstract

Objective

To investigate the role of lncRNA PlncRNA-1 in the pathogenesis of breast cancer.

Methods

A total of 78 patients with breast cancer as well as 48 healthy females were included in this study. Expression in tumor tissues and adjacent healthy tissues of breast cancer patients, as well as in breast tissues and serum of both patients and healthy control was detected by qRT-PCR. Cell proliferation was detected by CCK-8 assay, and cell apoptosis was tested by MTT assay. PlncRNA-1 overexpression cell lines were constructed and the effects on TGF-β1 as well as phosphoglycerate dehydrogenase (PHGDH) were explored by western blot.

Results

Expression levels of PlncRNA-1 were significantly lower in tumor tissues than those in adjacent healthy tissues. Significantly lower expression levels of PlncRNA-1 were also found in breast cancer patients than those in healthy controls in both breast tissue and serum. Upregulation of PlncRNA-1 promoted the expression of TGF-β1, but inhibited the expression of PHGDH. LncRNA PlncRNA-1 overexpression reduced the proliferation rate, but increased the apoptosis rate of breast cancer cells, while treatment with TGF-β inhibitor reduced those effects of PlncRNA-1 overexpression.

Conclusion

LncRNA PlncRNA-1 overexpression inhibits the growth of breast cancer by upregulating TGF-β1 and downregulating PHGDH.

https://ift.tt/2HfAPVz

2018 Presidential Address—Society of Surgical Oncology: The Fundamental Difference Between Cancer Treatment and Patient Care

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Prevalence and Predictors of Preoperative Venous Thromboembolism in Asymptomatic Patients Undergoing Major Oncologic Surgery

Abstract

Background

Postoperative venous thromboembolism (VTE) is a leading cause of in-hospital mortality for cancer patients; however, the prevalence of preoperative VTE remains unclear.

Objective

The aim of this study was to evaluate the prevalence and risk factors associated with preoperative VTE in asymptomatic patients undergoing major oncologic surgery.

Methods

Retrospective analysis of 346 patients identified from our prospectively maintained database of patients undergoing abdominopelvic oncologic surgery from 2009 to 2016.

Results

The prevalence of preoperative VTE found on screening venous duplex scan was 10.1%. Patients with a history of prior VTE were more likely to have a preoperative deep vein thrombosis (DVT) versus those with no prior VTE (42.9% vs. 4.5%, p < 0.01). Relative risk for prior VTE was 8.2 [95% confidence interval (CI) 4.7–14.3]. Older age was also associated with preoperative VTE. Regression modeling determined that patients were 1.24-fold as likely to have a preoperative DVT for every 5-year increase in age (relative risk 1.24, 95% CI 1.09–1.42). Patients with preoperative DVT were more likely to have been diagnosed with sepsis 1 month prior to surgery (8.6% vs. 1.6%, p = 0.04). There were no postoperative pulmonary emboli. The overall postoperative complication rate was higher in those with a preoperative DVT (25.7% vs. 13.2%, p = 0.071).

Conclusion

Asymptomatic patients undergoing major oncologic surgery have a 10.1% prevalence of preoperative DVT. Increasing age, recent diagnosis of sepsis, and a history of prior VTE are significantly associated with preoperative DVTs. This suggests high-risk oncologic patients may benefit from screening lower extremity venous duplex ultrasound prior to Surgery.

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Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy

Abstract

Background

We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT).

Methods

Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT.

Results

Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45–2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34–1.71) more likely than SNB followed by ALND.

Conclusions

Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

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Value of Preoperative PET-CT in the Prediction of Pathological Stage of Gastric Cancer

Abstract

Background

Preoperative precise staging is essential for the treatment of gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be increased. The present study investigated the clinical value of positron emission tomography-computed tomography (PET-CT) for the staging of GC.

Methods

This was a retrospective study of 117 patients with a clinical diagnosis of advanced GC who underwent PET-CT followed by gastrectomy. The incidence of FDG uptake in the primary tumor or lymph nodes and its relationship with clinicopathological factors, particularly pathological stage (pStage) III/IV, were examined.

Results

FDG uptake in the primary tumor was noted in 83 patients (70.9%). FDG uptake in the lymph nodes was detected in 21 patients (17.9%), and its sensitivity and specificity for lymph node metastasis were 22.7 and 90.5%, respectively. Multiple logistic regression analyses showed that FDG uptake in the primary tumor (odds ratio (OR) 2.764; 95% confidence interval (CI) 1.104–7.459, p = 0.029) and that in the lymph nodes (OR 4.660; 95% CI 1.675–13.84, p = 0.003) were factors independently associated with pStage III/IV. FDG uptake in the primary tumor detected pStage III/IV with higher sensitivity (80.4%) and that in lymph nodes found pStage III/IV with higher specificity (88.7%) than those of upper endoscopy plus CT (60.9 and 67.6%, respectively).

Conclusions

PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

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Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases

Abstract

Introduction

While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors.

Methods

All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not.

Results

Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0–136.0) vs. 107.0 months (95% CI 78.0–136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2–27.0) vs. 18.0 months (95% CI 13.8–22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9–128.6) vs. 65.0 months (95% CI 28.1–101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6–26.9) vs. 12.1 months (2.2–22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not.

Conclusions

The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

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Application of Serum Annexin A3 in Diagnosis, Outcome Prediction and Therapeutic Response Evaluation for Patients with Hepatocellular Carcinoma

Abstract

Purpose

Annexin A3 (ANXA3) could induce progression of hepatocellular carcinoma (HCC) via promoting stem cell traits of CD133-positive cells. Moreover, serum ANXA3 showed preliminary diagnostic potential, however further validation was required. Meanwhile, the prognostic value of ANXA3 remained elusive. The present study aimed to validate diagnostic performance and further systematically investigate the prognostic value of serum ANXA3.

Methods

Serum ANXA3 of 368 HCC patients was determined by enzyme-linked immunosorbent assay (ELISA); 295 of these patients underwent resection and 73 underwent transcatheter arterial chemoembolization (TACE). Diagnostic performance of ANXA3 was evaluated by receiver operating characteristic (ROC) analysis, and the prognostic value was evaluated by Cox regression and Kaplan–Meier analysis. To evaluate the relationship between serum ANXA3 and circulating CD133 mRNA-positive tumor cells (CD133^mRNA+ CTCs), real-time polymerase chain reaction was conducted in 69 patients who underwent resection.

Results

Serum ANXA3 provided greater diagnostic performance than α-fetoprotein (area under the curve [AUC] 0.869 vs. 0.782), especially in early diagnosis (AUC 0.852 vs. 0.757) and discriminating HCC from patients at risk (0.832 vs. 0.736). Pretreatment ANXA3 was an independent predictor of tumor recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, p = 0.002)/progression (HR 1.88, 95% CI 1.04–3.43, p = 0.038) and survival (resectable: HR 2.26, 95% CI 1.44–3.56, p = 0.001; unresectable: HR 2.08, 95% CI 1.10–4.05, p = 0.025), and retained its performance in low-recurrence-risk subgroups. Specifically, dynamic changes of ANXA3-positive status was associated with worse prognosis. ANXA3 was positively correlated with CD133^mRNA+ CTCs (r = 0.601, p < 0.001). In patients with detectable CD133^mRNA+ CTC, high ANXA3 was positively associated with a higher risk of recurrence and shorter overall survival.

Conclusions

Serum ANXA3 shows promise as a biomarker for diagnosis, outcome prediction, and therapeutic response evaluation in patients with HCC.

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Efficacy of the Gallbladder Cancer Predictive Risk Score Based on Pathological Findings: A Propensity Score-Matched Analysis

Abstract

Background

The optimal prognostic predictive system for gallbladder carcinoma (GBC) has not been established. The gallbladder cancer predictive risk score (GBRS) based on pathological findings identifies incidental GBC patients at risk of recurrence.

Objective

We aimed to validate the prognostic ability of the GBRS in all GBC patients following curative surgery.

Methods

Fifty-six patients with GBC who underwent curative surgery between 1996 and 2016 were included in this study. Univariate and multivariate analyses were performed to determine prognostic factors associated with overall and recurrence-free survival, and propensity score-matched analysis was performed.

Results

The median patient age was 71.9 years, and 39.3% of patients were males. All patients underwent curative surgery (33.9%, simple cholecystectomy; 66.1%, more advanced procedures, such as hepatectomy; and 32.1%, bile duct reconstruction). On univariate analysis, preoperative carbohydrate antigen 19-9 (CA19–9) ≥ 37 U/mL (p = 0.042), postoperative complications (p = 0.043), and a high GBRS (p < 0.001) were prognostic factors for worse overall survival. On multivariate analysis, CA19–9 ≥ 37 U/mL (p = 0.039 and p = 0.043, respectively) and a high GBRS (p = 0.001 and p = 0.010, respectively) were independent risk factors for poor overall and recurrence-free survival. After propensity score-matched analysis, the GBRS precisely predicted prognosis of patients with GBC.

Conclusions

The GBRS is an easy and novel prognostic predicting score. Our validation revealed good discrimination, suggesting its clinical utility to improve individualized prediction of survival for patients undergoing resection of GBC.

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Patterns of Treatment Failure in Patients with Sinonasal Mucosal Melanoma

Abstract

Background

Head and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites.

Objective

The purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure.

Methods

This study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models.

Results

The 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11–2.66; and HR 2.12, 95% CI 1.21–3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24–7.83; and HR 3.6, 95% CI 1.12–7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence.

Conclusion

The most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

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Prevalence and Predictors of Preoperative Venous Thromboembolism in Asymptomatic Patients Undergoing Major Oncologic Surgery

Abstract

Background

Postoperative venous thromboembolism (VTE) is a leading cause of in-hospital mortality for cancer patients; however, the prevalence of preoperative VTE remains unclear.

Objective

The aim of this study was to evaluate the prevalence and risk factors associated with preoperative VTE in asymptomatic patients undergoing major oncologic surgery.

Methods

Retrospective analysis of 346 patients identified from our prospectively maintained database of patients undergoing abdominopelvic oncologic surgery from 2009 to 2016.

Results

The prevalence of preoperative VTE found on screening venous duplex scan was 10.1%. Patients with a history of prior VTE were more likely to have a preoperative deep vein thrombosis (DVT) versus those with no prior VTE (42.9% vs. 4.5%, p < 0.01). Relative risk for prior VTE was 8.2 [95% confidence interval (CI) 4.7–14.3]. Older age was also associated with preoperative VTE. Regression modeling determined that patients were 1.24-fold as likely to have a preoperative DVT for every 5-year increase in age (relative risk 1.24, 95% CI 1.09–1.42). Patients with preoperative DVT were more likely to have been diagnosed with sepsis 1 month prior to surgery (8.6% vs. 1.6%, p = 0.04). There were no postoperative pulmonary emboli. The overall postoperative complication rate was higher in those with a preoperative DVT (25.7% vs. 13.2%, p = 0.071).

Conclusion

Asymptomatic patients undergoing major oncologic surgery have a 10.1% prevalence of preoperative DVT. Increasing age, recent diagnosis of sepsis, and a history of prior VTE are significantly associated with preoperative DVTs. This suggests high-risk oncologic patients may benefit from screening lower extremity venous duplex ultrasound prior to Surgery.

https://ift.tt/2qcOcyc

2018 Presidential Address—Society of Surgical Oncology: The Fundamental Difference Between Cancer Treatment and Patient Care

https://ift.tt/2uR0UI1

Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy

Abstract

Background

We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT).

Methods

Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT.

Results

Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45–2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34–1.71) more likely than SNB followed by ALND.

Conclusions

Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

https://ift.tt/2H0Lqpp

Value of Preoperative PET-CT in the Prediction of Pathological Stage of Gastric Cancer

Abstract

Background

Preoperative precise staging is essential for the treatment of gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be increased. The present study investigated the clinical value of positron emission tomography-computed tomography (PET-CT) for the staging of GC.

Methods

This was a retrospective study of 117 patients with a clinical diagnosis of advanced GC who underwent PET-CT followed by gastrectomy. The incidence of FDG uptake in the primary tumor or lymph nodes and its relationship with clinicopathological factors, particularly pathological stage (pStage) III/IV, were examined.

Results

FDG uptake in the primary tumor was noted in 83 patients (70.9%). FDG uptake in the lymph nodes was detected in 21 patients (17.9%), and its sensitivity and specificity for lymph node metastasis were 22.7 and 90.5%, respectively. Multiple logistic regression analyses showed that FDG uptake in the primary tumor (odds ratio (OR) 2.764; 95% confidence interval (CI) 1.104–7.459, p = 0.029) and that in the lymph nodes (OR 4.660; 95% CI 1.675–13.84, p = 0.003) were factors independently associated with pStage III/IV. FDG uptake in the primary tumor detected pStage III/IV with higher sensitivity (80.4%) and that in lymph nodes found pStage III/IV with higher specificity (88.7%) than those of upper endoscopy plus CT (60.9 and 67.6%, respectively).

Conclusions

PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

https://ift.tt/2uRTnZ9

Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases

Abstract

Introduction

While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors.

Methods

All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not.

Results

Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0–136.0) vs. 107.0 months (95% CI 78.0–136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2–27.0) vs. 18.0 months (95% CI 13.8–22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9–128.6) vs. 65.0 months (95% CI 28.1–101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6–26.9) vs. 12.1 months (2.2–22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not.

Conclusions

The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

https://ift.tt/2H50S3Z

Application of Serum Annexin A3 in Diagnosis, Outcome Prediction and Therapeutic Response Evaluation for Patients with Hepatocellular Carcinoma

Abstract

Purpose

Annexin A3 (ANXA3) could induce progression of hepatocellular carcinoma (HCC) via promoting stem cell traits of CD133-positive cells. Moreover, serum ANXA3 showed preliminary diagnostic potential, however further validation was required. Meanwhile, the prognostic value of ANXA3 remained elusive. The present study aimed to validate diagnostic performance and further systematically investigate the prognostic value of serum ANXA3.

Methods

Serum ANXA3 of 368 HCC patients was determined by enzyme-linked immunosorbent assay (ELISA); 295 of these patients underwent resection and 73 underwent transcatheter arterial chemoembolization (TACE). Diagnostic performance of ANXA3 was evaluated by receiver operating characteristic (ROC) analysis, and the prognostic value was evaluated by Cox regression and Kaplan–Meier analysis. To evaluate the relationship between serum ANXA3 and circulating CD133 mRNA-positive tumor cells (CD133^mRNA+ CTCs), real-time polymerase chain reaction was conducted in 69 patients who underwent resection.

Results

Serum ANXA3 provided greater diagnostic performance than α-fetoprotein (area under the curve [AUC] 0.869 vs. 0.782), especially in early diagnosis (AUC 0.852 vs. 0.757) and discriminating HCC from patients at risk (0.832 vs. 0.736). Pretreatment ANXA3 was an independent predictor of tumor recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, p = 0.002)/progression (HR 1.88, 95% CI 1.04–3.43, p = 0.038) and survival (resectable: HR 2.26, 95% CI 1.44–3.56, p = 0.001; unresectable: HR 2.08, 95% CI 1.10–4.05, p = 0.025), and retained its performance in low-recurrence-risk subgroups. Specifically, dynamic changes of ANXA3-positive status was associated with worse prognosis. ANXA3 was positively correlated with CD133^mRNA+ CTCs (r = 0.601, p < 0.001). In patients with detectable CD133^mRNA+ CTC, high ANXA3 was positively associated with a higher risk of recurrence and shorter overall survival.

Conclusions

Serum ANXA3 shows promise as a biomarker for diagnosis, outcome prediction, and therapeutic response evaluation in patients with HCC.

https://ift.tt/2IBEYme

Efficacy of the Gallbladder Cancer Predictive Risk Score Based on Pathological Findings: A Propensity Score-Matched Analysis

Abstract

Background

The optimal prognostic predictive system for gallbladder carcinoma (GBC) has not been established. The gallbladder cancer predictive risk score (GBRS) based on pathological findings identifies incidental GBC patients at risk of recurrence.

Objective

We aimed to validate the prognostic ability of the GBRS in all GBC patients following curative surgery.

Methods

Fifty-six patients with GBC who underwent curative surgery between 1996 and 2016 were included in this study. Univariate and multivariate analyses were performed to determine prognostic factors associated with overall and recurrence-free survival, and propensity score-matched analysis was performed.

Results

The median patient age was 71.9 years, and 39.3% of patients were males. All patients underwent curative surgery (33.9%, simple cholecystectomy; 66.1%, more advanced procedures, such as hepatectomy; and 32.1%, bile duct reconstruction). On univariate analysis, preoperative carbohydrate antigen 19-9 (CA19–9) ≥ 37 U/mL (p = 0.042), postoperative complications (p = 0.043), and a high GBRS (p < 0.001) were prognostic factors for worse overall survival. On multivariate analysis, CA19–9 ≥ 37 U/mL (p = 0.039 and p = 0.043, respectively) and a high GBRS (p = 0.001 and p = 0.010, respectively) were independent risk factors for poor overall and recurrence-free survival. After propensity score-matched analysis, the GBRS precisely predicted prognosis of patients with GBC.

Conclusions

The GBRS is an easy and novel prognostic predicting score. Our validation revealed good discrimination, suggesting its clinical utility to improve individualized prediction of survival for patients undergoing resection of GBC.

https://ift.tt/2qaUrmo

Patterns of Treatment Failure in Patients with Sinonasal Mucosal Melanoma

Abstract

Background

Head and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites.

Objective

The purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure.

Methods

This study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models.

Results

The 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11–2.66; and HR 2.12, 95% CI 1.21–3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24–7.83; and HR 3.6, 95% CI 1.12–7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence.

Conclusion

The most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

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Disparities in the survivorship experience among Latina survivors of breast cancer

Cancer, EarlyView.


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Temporal trends in disease presentation and survival of patients with hepatocellular carcinoma: A real‐world experience from 1998 to 2015

Cancer, EarlyView.


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Feasibility, safety, and efficacy of aerobic training in pretreated patients with metastatic breast cancer: A randomized controlled trial

Cancer, EarlyView.


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Symptoms of anxiety and depression among colorectal cancer survivors from the population‐based, longitudinal PROFILES Registry: Prevalence, predictors, and impact on quality of life

Cancer, EarlyView.


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Alternative payment and care‐delivery models in oncology: A systematic review

Cancer, EarlyView.


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Disparities in the survivorship experience among Latina survivors of breast cancer

Cancer, EarlyView.


https://ift.tt/2GKkEP2

Temporal trends in disease presentation and survival of patients with hepatocellular carcinoma: A real‐world experience from 1998 to 2015

Cancer, EarlyView.


https://ift.tt/2H1veo8

Feasibility, safety, and efficacy of aerobic training in pretreated patients with metastatic breast cancer: A randomized controlled trial

Cancer, EarlyView.


https://ift.tt/2GHlV9x

Symptoms of anxiety and depression among colorectal cancer survivors from the population‐based, longitudinal PROFILES Registry: Prevalence, predictors, and impact on quality of life

Cancer, EarlyView.


https://ift.tt/2H0ZUWg

Alternative payment and care‐delivery models in oncology: A systematic review

Cancer, EarlyView.


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Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations

Publication date: Available online 5 April 2018
Source:Cancer/Radiothérapie
Author(s): J. Langrand-Escure, R. de Crevoisier, C. Llagostera, G. Créhange, G. Delaroche, C. Lafond, C. Bonin, F. Bideault, P. Sargos, S. Belhomme, D. Pasquier, I. Latorzeff, S. Supiot, C. Hennequin
Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques.



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Évaluation d’un logiciel pour la délinéation automatique des organes à risques et des volumes cibles ganglionnaires chez des patientes prises en charge pour un cancer du sein

Publication date: Available online 5 April 2018
Source:Cancer/Radiothérapie
Author(s): A. Arsène-Henry, H.-P. Xu, M. Robilliard, W. El Amine, É. Costa, Y.M. Kirova
Objectif de l'étudeLa radiothérapie conformationelle avec modulation d'intensité implique une délinéation précise des volumes d'intérêt et par conséquent une augmentation du temps consacré à la délinéation. L'objectif de cette étude était d'évaluer le logiciel de délinéation automatique Workflow Box (Mirada Medical, Royaume-Uni) pour les organes à risque et les volumes cibles ganglionnaires chez des patientes prises en charge pour un cancer du sein.Matériel et méthodesVingt dossiers de patientes prises en charge pour un cancer du sein délinéé selon les recommandations de l'European Society for Radiotherapy and Oncology ont permis la création d'un atlas dans le logiciel de délinéation automatique. Puis trente autres dossiers ont été délinéés à la fois par le logiciel et par un oncologue-radiothérapeute (contours de référence). La précision des contours a été évaluée avec l'indice overlap volume et les écarts-types (ET).RésultatsEn ce qui concerne les organes à risque, les moyennes des overlap volumes s'étalaient de 0,49 (ET=0,21) à 0,97 (ET=0,03). Cinq organes à risque sur neuf avaient un overlap volume supérieur ou égal à 0,8. L'overlap volume moyen pour l'ensemble des organes à risque était de 0,77 (ET=0,17). Le logiciel était moins performant pour les volumes cibles avec un overlap volume moyen de 0,43 (ET=0,1) et s'étalant de 0,23 (ET=0,13) à 0,52 (ET=0,1). Le logiciel a permis de diminuer de 40 % le temps moyen de délinéation par patiente.ConclusionPour des cas de cancers du sein, le logiciel de délinéation automatique Workflow Box a permis un gain de temps dans l'étape de délinéation en produisant notamment des contours d'organes à risque fiables. Cependant, il reste insuffisant en ce qui concerne les volumes cibles ganglionnaires. Une nouvelle évaluation est prévue après le début d'utilisation de ce logiciel de délinéation dans la pratique quotidienne.PurposeIntensity-modulated radiotherapy needs the strict delineation of target volumes as well as organs at risk and the time used for this procedure is long. The purpose of this study was to evaluate the Workflow Box system (Mirada Medical, UK) for automatic delineation and segmentation for everyday use of organs at risk and lymph nodes delineation in patients treated for early stage breast cancer.Material and methodsTwenty patients' CT scans in treatment position for their breast cancer radiotherapy were delineated in respect of the ESTRO delineation guidelines to begin the creation of automatic delineation atlas. Then 30 other CT scans were delineated this time by the automatic delineation system and by the radiation oncologist (reference delineation plan). The precision of the delineation was evaluated using the overlap volume index and evaluation of standard deviation (SD).ResultsThe study of organs at risk has shown that the mean overlap volumes were between 0.49 (SD=0.21) and 0.97 (ET=0.03). Five organs at risk out of nine had overlap volumes at least 0.8. The mean overlap volume for all organs at risk was 0.77 (SD=0.17). The system was less performing for the lymph nodes with a mean overlap volume of 0.43 (SD=0.1) and ranging between 0.23 (SD=0.13) and 0.52 (SD=0.1). The use of this system reduced the delineation time by 40% per patient.ConclusionsFor patients with breast cancer, the system for automatic delineation and segmentation Workflow Box (Mirada Medical, UK) permitted to safely shorten the time for delineation with acceptable organs at risk delineation. Improvement of lymph node volumes is needed. A new evaluation will be realized after using the system in routine practice.



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Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie

Publication date: Available online 6 April 2018
Source:Cancer/Radiothérapie
Author(s): Y. Brahimi, D. Antoni, R. Srour, F. Proust, H. Cebula, A. Labani, G. Noël




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Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations

Publication date: Available online 5 April 2018
Source:Cancer/Radiothérapie
Author(s): J. Langrand-Escure, R. de Crevoisier, C. Llagostera, G. Créhange, G. Delaroche, C. Lafond, C. Bonin, F. Bideault, P. Sargos, S. Belhomme, D. Pasquier, I. Latorzeff, S. Supiot, C. Hennequin
Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques.



https://ift.tt/2GVKhQf

Évaluation d’un logiciel pour la délinéation automatique des organes à risques et des volumes cibles ganglionnaires chez des patientes prises en charge pour un cancer du sein

Publication date: Available online 5 April 2018
Source:Cancer/Radiothérapie
Author(s): A. Arsène-Henry, H.-P. Xu, M. Robilliard, W. El Amine, É. Costa, Y.M. Kirova
Objectif de l'étudeLa radiothérapie conformationelle avec modulation d'intensité implique une délinéation précise des volumes d'intérêt et par conséquent une augmentation du temps consacré à la délinéation. L'objectif de cette étude était d'évaluer le logiciel de délinéation automatique Workflow Box (Mirada Medical, Royaume-Uni) pour les organes à risque et les volumes cibles ganglionnaires chez des patientes prises en charge pour un cancer du sein.Matériel et méthodesVingt dossiers de patientes prises en charge pour un cancer du sein délinéé selon les recommandations de l'European Society for Radiotherapy and Oncology ont permis la création d'un atlas dans le logiciel de délinéation automatique. Puis trente autres dossiers ont été délinéés à la fois par le logiciel et par un oncologue-radiothérapeute (contours de référence). La précision des contours a été évaluée avec l'indice overlap volume et les écarts-types (ET).RésultatsEn ce qui concerne les organes à risque, les moyennes des overlap volumes s'étalaient de 0,49 (ET=0,21) à 0,97 (ET=0,03). Cinq organes à risque sur neuf avaient un overlap volume supérieur ou égal à 0,8. L'overlap volume moyen pour l'ensemble des organes à risque était de 0,77 (ET=0,17). Le logiciel était moins performant pour les volumes cibles avec un overlap volume moyen de 0,43 (ET=0,1) et s'étalant de 0,23 (ET=0,13) à 0,52 (ET=0,1). Le logiciel a permis de diminuer de 40 % le temps moyen de délinéation par patiente.ConclusionPour des cas de cancers du sein, le logiciel de délinéation automatique Workflow Box a permis un gain de temps dans l'étape de délinéation en produisant notamment des contours d'organes à risque fiables. Cependant, il reste insuffisant en ce qui concerne les volumes cibles ganglionnaires. Une nouvelle évaluation est prévue après le début d'utilisation de ce logiciel de délinéation dans la pratique quotidienne.PurposeIntensity-modulated radiotherapy needs the strict delineation of target volumes as well as organs at risk and the time used for this procedure is long. The purpose of this study was to evaluate the Workflow Box system (Mirada Medical, UK) for automatic delineation and segmentation for everyday use of organs at risk and lymph nodes delineation in patients treated for early stage breast cancer.Material and methodsTwenty patients' CT scans in treatment position for their breast cancer radiotherapy were delineated in respect of the ESTRO delineation guidelines to begin the creation of automatic delineation atlas. Then 30 other CT scans were delineated this time by the automatic delineation system and by the radiation oncologist (reference delineation plan). The precision of the delineation was evaluated using the overlap volume index and evaluation of standard deviation (SD).ResultsThe study of organs at risk has shown that the mean overlap volumes were between 0.49 (SD=0.21) and 0.97 (ET=0.03). Five organs at risk out of nine had overlap volumes at least 0.8. The mean overlap volume for all organs at risk was 0.77 (SD=0.17). The system was less performing for the lymph nodes with a mean overlap volume of 0.43 (SD=0.1) and ranging between 0.23 (SD=0.13) and 0.52 (SD=0.1). The use of this system reduced the delineation time by 40% per patient.ConclusionsFor patients with breast cancer, the system for automatic delineation and segmentation Workflow Box (Mirada Medical, UK) permitted to safely shorten the time for delineation with acceptable organs at risk delineation. Improvement of lymph node volumes is needed. A new evaluation will be realized after using the system in routine practice.



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Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie

Publication date: Available online 6 April 2018
Source:Cancer/Radiothérapie
Author(s): Y. Brahimi, D. Antoni, R. Srour, F. Proust, H. Cebula, A. Labani, G. Noël




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Differences in recurrence and survival of extremity liposarcoma subtypes

Publication date: Available online 6 April 2018
Source:European Journal of Surgical Oncology
Author(s): M. Vos, H. Koseła-Paterczyk, P. Rutkowski, G.J.L.H. van Leenders, M. Normantowicz, A. Lecyk, S. Sleijfer, C. Verhoef, D.J. Grünhagen
BackgroundLiposarcomas can be divided into four subtypes and are most frequently located in the extremities. There are currently no studies comparing the clinical outcomes, such as local recurrence and distant metastasis, between the distinct subtypes of primary LPS of the extremity specifically.MethodsRetrospective databases of two expertise centres (Rotterdam-R, Warsaw-W) of patients with liposarcoma located in the extremities from 1985-2015 were used to analyse 5-year local recurrence-free survival (5y-LRFS), 5-year distant metastasis-free survival (5y-DMFS) and 5-year overall survival (5y-OS).ResultsWe identified 456 patients: 192 well-differentiated liposarcomas (WDLPS), 172 myxoid liposarcomas (MLPS), 54 pleomorphic liposarcomas (PLPS), 23 dedifferentiated liposarcomas (DDLPS) and 15 other subtypes. The frequency of (neo)adjuvant radiotherapy (R: 34.5% vs. W: 78.4%) and R0-resections (R: 41.0% vs. W: 84.1%) differed between the datasets. Local recurrences (LR) were observed most frequently in DDLPS (5y-LRFS 62.4%), followed by PLPS (71.4%), WDLPS (77.0%) and MLPS (84.5%, p=0.054). Distant metastases (DM) were most commonly observed in PLPS (5y-DMFS 46.9%), followed by MLPS (74.0%), DDLPS (86.3%) and WDLPS (97.3%). 5y-OS was poorest in patients with PLPS (47.6%) and DDLPS (54.4%), followed by MLPS (79.7%) and WDLPS (92.4%, p<0.001). Male gender significantly increased the risk of LR and DM. The subtypes MLPS and PLPS were significant prognostic factors for DM and OS. Additionally, DDLPS and age had significant impact on OS.ConclusionIn the largest cohort of extremity LPS patients reported to date, LPS subtypes show distinct patterns of LR, DM and OS, stressing that 'extremity LPS' is not a single entity. Parts of this abstract were presented as a poster at the annual meeting of the CTOS in Lisbon, November 2016 and at the annual meeting of the ESMO in Madrid, September 2017 where it was awarded with the 'Best Poster' award.



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Long-term outcomes of laparoscopic versus open D3 dissection for stage II/III colon cancer: Results of propensity score analyses

Publication date: Available online 5 April 2018
Source:European Journal of Surgical Oncology
Author(s): Dai Shida, Hiroki Ochiai, Shunsuke Tsukamoto, Yukihide Kanemitsu
BackgroundNon-inferiority of the laparoscopic approach for stage II/III colon cancer has not been clearly established. This study aimed to evaluate the long-term outcomes of laparoscopic versus open D3 surgery.MethodsSubjects were 1230 consecutive patients with stage II/III colon cancer, who were referred to the National Cancer Center Hospital from 2004 to 2013. Open surgery was performed in 821 (67%) patients, and laparoscopic surgery was performed in 409 (33%). Propensity score analyses with overall survival as the primary endpoint were performed in three different propensity score methods.ResultsRegression adjustment using the propensity score as a linear predictor in the model showed similar overall survival between laparoscopic and open surgeries [hazard ratio (HR), 0.98 (95% CI [0.64 – 1.46]; p=0.916)]. Stratification analysis of the entire cohort revealed that, among five strata, only the highest stratum (clinical T2/T3, clinical N0/N1, tumor size <6 cm, and body mass index (BMI) < 28) had an HR of <1 (0.37). In the other four strata, open surgery was favored as reflected by HRs of >1 (1.13-1.26). The propensity score-matched cohort (365 matched pairs), from which patients with advanced disease and high BMI were excluded, yielded an HR of 0.93 (95% CI [0.57 – 1.52]; p=0.772).ConclusionsLaparoscopic surgery appeared to be a safe and reasonable option for patients with stage II/III colon cancer in general. Patients with high BMI, clinical N2 and T4 disease, and tumor size ≥6 cm might require prudent selection of surgical approach.



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Contribution of lymph node staging method and prognostic factors in malignant ovarian sex cord-stromal tumors: a world wide database analysis

Publication date: Available online 6 April 2018
Source:European Journal of Surgical Oncology
Author(s): Jieyu Wang, Jun Li, Ruifang Chen, Xin Lu
ObjectiveTo investigate the clinicopathologic prognostic factors in patients with malignant sex cord-stromal tumors (SCSTs) with lymph node dissection, and at the same time, to evaluate the influence of the log odds of positive lymph nodes (LODDS) on their survival.MethodsPatients diagnosed with malignant SCSTs who underwent lymph node dissection were extracted from the 1988-2013 Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier curves. The Cox proportional hazards regression model was used to identify independent predictors of survival.Results576 patients with malignant SCSTs and with lymphadenectomy were identified, including 468 (81.3%) patients with granulosa cell tumors (GCTs) and 80 (13.9%) patients with Sertoli-Leydig cell tumors (SLCTs). 399 (69.3%) patients and 118 (20.5%) patients were in the LODDS˂-1 group and -1≤LODDS˂-0.5 group, respectively. The 10-year OS rate was 80.9% and CSS was 87.2% in the LODDS˂-0.5 group, whereas the survival rates for other groups were 68.5% and 73.3%. On multivariate analysis, age 50 years or less (p˂0.001), tumor size of 10cm or less (p˂0.001), early-stage disease (p<0.001), and GCT histology (p≤0.001) were the significant prognostic factors for improved survival. LODDS ˂-0.5 was associated with a favorable prognosis (OS: p = 0.051; CSS:P = 0.055).ConclusionsYounger age, smaller tumor size, early stage, and GCT histologic type are independent prognostic factors for improved survival in patients with malignant SCST with lymphadenectomy. Stratified LODDS could be regarded as an effective value to assess the lymph node status, and to predict the survival status of patients.



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Theragnostic target, prostate-specific membrane antigen—also specific for non-prostatic malignancies

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Marigdalia K. Ramirez-Fort, Sean S. Mahase, Joseph R. Osborne, Christopher S. Lange




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Dosimetric evaluation of incorporating patient geometric variations into adaptive plan optimization through probabilistic treatment planning in head-and-neck cancers

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Qiang Liu, Jian Liang, Dingyi Zhou, Daniel J. Krauss, Peter Y. Chen, Di Yan
Purpose4D adaptive treatment planning (4D ART) is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from CT or cone-beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization through a probabilistic treatment planning method. The goal of this planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head-and-neck (HN) cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions according to existing normal tissue complication probability (NTCP) models.Methods and MaterialsFor 18 HN cancer patients, treatment plans were retrospectively generated for four different treatment strategies, including a solely image-guided radiotherapy (IGRT) strategy (IGRT-only), two conventional adaptive planning strategies using 3- and 0-mm planning target volume (PTV) margins (3-mm ART and 0-mm ART), respectively, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied during the entire treatment course. In the two conventional adaptive strategies, two new treatment plans were generated during the treatment course using diagnostic planning CTs acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule except that the 4D adaptive plan was generated using 5 CBCT images that were acquired over the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCTs, deforming back to the pre-treatment planning CT and accumulating over all 35 fractions. The target coverage was evaluated using V100% (the percentage target volume receiving ≥100% prescription dose) and D99 (the minimum dose to 99% target volume). It was considered adequate if V100% was ≥95% and dose deficit in D99 was ≤2 Gy (with respect to the prescription dose). For each strategy, the dose received by organs-at-risk (OARs) was also evaluated and corresponding NTCP values were subsequently calculated using three NTCP models.ResultsAdequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with 3-mm PTV margin regardless of adaptation. 3-mm ART reduced OAR mean doses (Dmean) by 1-2 Gy over IGRT-only. 0-mm ART further reduced OAR dose by another 2-3 Gy at the expense of target coverage: 3 and 1 patients had V100% <95%, 6 and 5 patients had >2 Gy dose deficit in D99, for CTV1 and CTV2, respectively. 4D ART improved target coverage while attaining similar OAR sparing as 0-mm ART: the number of patients that had V100% <95% and >2 Gy D99 deficit dropped to 0 and 0 for CTV1, 0 and 2 for CTV2, respectively. NTCP calculations suggested that 4D ART could benefit a substantial portion of patients as compare to IGRT-only (e.g., 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity, 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively).ConclusionsCompared to margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicts theoretical clinical benefits that warrant further clinical validation.

Teaser

Dosimetric benefit of incorporating patient geometric variations into offline adaptive plan optimization through probabilistic treatment planning was investigated in head-and-neck cancer patients. The study results demonstrate that this novel adaptive planning approach (4D ART) can achieve improved organ-at-risk sparing while maintaining adequate target coverage.


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Clinical outcomes for patients with Gleason Score 10 prostate adenocarcinoma: results from a multi-institutional consortium study

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kiri A. Sandler, Ryan R. Cook, Jay P. Ciezki, Ashley E. Ross, Mark M. Pomerantz, Paul L. Nguyen, Talha Shaikh, Phuoc T. Tran, Richard G. Stock, Gregory S. Merrick, D. Jeffrey Demanes, Daniel E. Spratt, Eyad I. Abu-Isa, Trude B. Wedde, Wolfgang Lilleby, Daniel J. Krauss, Grace K. Shaw, Ridwan Alam, Chandana A. Reddy, Daniel Y. Song, Eric A. Klein, Andrew J. Stephenson, Jeffrey J. Tosoian, John V. Hegde, Sun Mi Yoo, Ryan Fiano, Anthony V. D'Amico, Nicholas G. Nickols, William J. Aronson, Ahmad Sadeghi, Stephen C. Greco, Curtiland Deville, Todd McNutt, Theodore L. DeWeese, Robert E. Reiter, Jonathan W. Said, Michael L. Steinberg, Eric M. Horwitz, Patrick A. Kupelian, Christopher R. King, Amar U. Kishan
BackgroundGleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis for patients presenting with GS 10 PCa are largely unknown due to its rarity.Methods112 patients with biopsy GS 10 PCa who received treatment with radical prostatectomy (RP, n=26), external beam radiotherapy (EBRT, n=48), and EBRT with a brachytherapy boost (EBRT+BT, n=38) between 2000-2013 were included. Propensity scores were included as covariates for comparative analysis. Overall survival (OS), prostate cancer-specific survival (PCSS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding.ResultsThe median follow-up was 4.9 years overall (3.9 for RP, 4.8 for EBRT, and 5.7 for EBRT+BT). Significantly more EBRT than EBRT+BT patients received upfront ADT (98% vs 79%, p<0.01 by Chi square), though durations were similar (median 24 and 22.5 months, respectively). Thirty-four percent of RP patients received postoperative EBRT, and 35% received neoadjuvant systemic therapy. Propensity score-adjusted 5-year OS was 80% for the RP group, 73% for the EBRT group, and 83% for EBRT+BT group. Corresponding adjusted 5-year PCSS rates were 87%, 75%, and 94%, respectively. EBRT+BT trended toward superior DMFS when compared with RP (HR 0.3, 95% CI 0.1-1.06, p = .06) and had superior DMFS when compared with EBRT (HR 0.4, 95% CI 0.1-0.99, p = .048).ConclusionsTo our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease five years following treatment.

Teaser

Gleason 10 prostate cancer is extremely aggressive, and clinical outcomes are largely unknown due to its rarity. This study provides benchmark clinical outcomes information for patients with Gleason 10 prostate cancer with data extracted from a large multi-institutional database. Though it follows an aggressive course, the majority of patients are free from disease at 5 years, and there may be benefits to treating with radiation and brachytherapy.


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Theragnostic target, prostate-specific membrane antigen—also specific for non-prostatic malignancies

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Marigdalia K. Ramirez-Fort, Sean S. Mahase, Joseph R. Osborne, Christopher S. Lange




https://ift.tt/2HgfU4L

Dosimetric evaluation of incorporating patient geometric variations into adaptive plan optimization through probabilistic treatment planning in head-and-neck cancers

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Qiang Liu, Jian Liang, Dingyi Zhou, Daniel J. Krauss, Peter Y. Chen, Di Yan
Purpose4D adaptive treatment planning (4D ART) is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from CT or cone-beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization through a probabilistic treatment planning method. The goal of this planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head-and-neck (HN) cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions according to existing normal tissue complication probability (NTCP) models.Methods and MaterialsFor 18 HN cancer patients, treatment plans were retrospectively generated for four different treatment strategies, including a solely image-guided radiotherapy (IGRT) strategy (IGRT-only), two conventional adaptive planning strategies using 3- and 0-mm planning target volume (PTV) margins (3-mm ART and 0-mm ART), respectively, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied during the entire treatment course. In the two conventional adaptive strategies, two new treatment plans were generated during the treatment course using diagnostic planning CTs acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule except that the 4D adaptive plan was generated using 5 CBCT images that were acquired over the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCTs, deforming back to the pre-treatment planning CT and accumulating over all 35 fractions. The target coverage was evaluated using V100% (the percentage target volume receiving ≥100% prescription dose) and D99 (the minimum dose to 99% target volume). It was considered adequate if V100% was ≥95% and dose deficit in D99 was ≤2 Gy (with respect to the prescription dose). For each strategy, the dose received by organs-at-risk (OARs) was also evaluated and corresponding NTCP values were subsequently calculated using three NTCP models.ResultsAdequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with 3-mm PTV margin regardless of adaptation. 3-mm ART reduced OAR mean doses (Dmean) by 1-2 Gy over IGRT-only. 0-mm ART further reduced OAR dose by another 2-3 Gy at the expense of target coverage: 3 and 1 patients had V100% <95%, 6 and 5 patients had >2 Gy dose deficit in D99, for CTV1 and CTV2, respectively. 4D ART improved target coverage while attaining similar OAR sparing as 0-mm ART: the number of patients that had V100% <95% and >2 Gy D99 deficit dropped to 0 and 0 for CTV1, 0 and 2 for CTV2, respectively. NTCP calculations suggested that 4D ART could benefit a substantial portion of patients as compare to IGRT-only (e.g., 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity, 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively).ConclusionsCompared to margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicts theoretical clinical benefits that warrant further clinical validation.

Teaser

Dosimetric benefit of incorporating patient geometric variations into offline adaptive plan optimization through probabilistic treatment planning was investigated in head-and-neck cancer patients. The study results demonstrate that this novel adaptive planning approach (4D ART) can achieve improved organ-at-risk sparing while maintaining adequate target coverage.


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Clinical outcomes for patients with Gleason Score 10 prostate adenocarcinoma: results from a multi-institutional consortium study

Publication date: Available online 5 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kiri A. Sandler, Ryan R. Cook, Jay P. Ciezki, Ashley E. Ross, Mark M. Pomerantz, Paul L. Nguyen, Talha Shaikh, Phuoc T. Tran, Richard G. Stock, Gregory S. Merrick, D. Jeffrey Demanes, Daniel E. Spratt, Eyad I. Abu-Isa, Trude B. Wedde, Wolfgang Lilleby, Daniel J. Krauss, Grace K. Shaw, Ridwan Alam, Chandana A. Reddy, Daniel Y. Song, Eric A. Klein, Andrew J. Stephenson, Jeffrey J. Tosoian, John V. Hegde, Sun Mi Yoo, Ryan Fiano, Anthony V. D'Amico, Nicholas G. Nickols, William J. Aronson, Ahmad Sadeghi, Stephen C. Greco, Curtiland Deville, Todd McNutt, Theodore L. DeWeese, Robert E. Reiter, Jonathan W. Said, Michael L. Steinberg, Eric M. Horwitz, Patrick A. Kupelian, Christopher R. King, Amar U. Kishan
BackgroundGleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis for patients presenting with GS 10 PCa are largely unknown due to its rarity.Methods112 patients with biopsy GS 10 PCa who received treatment with radical prostatectomy (RP, n=26), external beam radiotherapy (EBRT, n=48), and EBRT with a brachytherapy boost (EBRT+BT, n=38) between 2000-2013 were included. Propensity scores were included as covariates for comparative analysis. Overall survival (OS), prostate cancer-specific survival (PCSS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding.ResultsThe median follow-up was 4.9 years overall (3.9 for RP, 4.8 for EBRT, and 5.7 for EBRT+BT). Significantly more EBRT than EBRT+BT patients received upfront ADT (98% vs 79%, p<0.01 by Chi square), though durations were similar (median 24 and 22.5 months, respectively). Thirty-four percent of RP patients received postoperative EBRT, and 35% received neoadjuvant systemic therapy. Propensity score-adjusted 5-year OS was 80% for the RP group, 73% for the EBRT group, and 83% for EBRT+BT group. Corresponding adjusted 5-year PCSS rates were 87%, 75%, and 94%, respectively. EBRT+BT trended toward superior DMFS when compared with RP (HR 0.3, 95% CI 0.1-1.06, p = .06) and had superior DMFS when compared with EBRT (HR 0.4, 95% CI 0.1-0.99, p = .048).ConclusionsTo our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease five years following treatment.

Teaser

Gleason 10 prostate cancer is extremely aggressive, and clinical outcomes are largely unknown due to its rarity. This study provides benchmark clinical outcomes information for patients with Gleason 10 prostate cancer with data extracted from a large multi-institutional database. Though it follows an aggressive course, the majority of patients are free from disease at 5 years, and there may be benefits to treating with radiation and brachytherapy.


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