Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Neoplasm, Residual

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Neoplastic Processes

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Herbal and Botanical

Pancrelipase

Pancreatin

Orange

After performing the pancreaticoduodenectomies, the surgeon intraoperatively inked the surfaces/margins of the specimen with different colours. The surfaces/margins inked were the following:

1. Anterior surface of the pancreas (yellow);
2. Posterior surface of the pancreas (orange);
3. Superior mesenteric/portal vein groove (blu);
4. Superior mesenteric artery margin (retroperitoneal margin) (red);
5. Transection margin of the bile duct (green) The trans-section pancreatic and gastric margins were not inked.

In arm B, only the superior mesenteric artery margin and the pancreatic margin were intraoperatively indicated by the surgeon in the specimen: a single stitch to identify the transection pancreatic margin and a continuous suture to identify the superior mesenteric artery margin. Monochromatic inking of the superior mesenteric artery margin was subsequently carried out by the pathologist.

Multicolour inking specimens

Monocolour inking specimens

Riccardo Casadei, Professor

A single-centre, randomised clinical trial of patients affected by periampullary cancer who underwent pancreaticoduodenectomies which included two different types of specimen margination: arm A (multicolour inking) and arm B (monocolour inking). The randomisation of the specimen was made after the resection, blinded for the surgeons involved in the operation. The primary endpoint was the overall R1 resection rate and its difference between the two arms. The secondary endpoints were the R1 resection rate in each margin and its difference between the two arms, and the impact of margin status on survival. A sample size of 18 patients was required.

This study was a single-centre, prospective, controlled, open, parallel group, randomised clinical trial, conducted in the tertiary referral University Centre of S.Orsola-Malpighi Hospital, Bologna, Italy, from June 2012 to January 2016, which enrolled patients affected by periampullary cancer who underwent pancreaticoduodenectomy (PD). All patients with suspected periampullary cancer were enrolled in the study, but only patients who underwent pancreaticoduodenectomy were randomised and allocated to a multicolour inking specimen (arm A, experimental) or a monocolour inking (arm B, control) after specimen was taken out from the operative field. The analysis regarded only the specimens of the patients who underwent PD in which the final pathologic report showed a diagnosis of invasive periampullary cancer (pancreatic, ampullary and distal bile duct).

After performing the pancreaticoduodenectomies, the surgeon intraoperatively inked the surfaces/margins of the specimen with different colours. In the multicolour arm, the surfaces/margins inked were the following: Anterior surface of the pancreas (yellow); Posterior surface of the pancreas (orange); Superior mesenteric/portal vein groove (blu); Superior mesenteric artery margin (retroperitoneal margin) (red); Transection margin of the bile duct (green).The trans-section pancreatic and gastric margins were not inked.

In the monocolour arm, only the superior mesenteric artery margin and the pancreatic margin were intraoperatively indicated by the surgeon in the specimen: a single stitch to identify the transection pancreatic margin and a continuous suture to identify the superior mesenteric artery margin. Monochromatic inking of the superior mesenteric artery margin was subsequently carried out by the pathologist. In both arms of treatment, the macroscopic evaluation and slicing of the surgical specimen followed the Leeds Pathology Protocol (LEEPP), and seven margins, which included the anterior, posterior, superior mesenteric /portal vein groove, superior mesenteric artery, bile duct, pancreatic neck and stomach margins, were examined. The primary endpoint was to evaluate the overall R1 resection rate and its difference between multicolour (arm A) and monocolour (arm B) inking of the specimen. The secondary endpoints were to evaluate the R1 resection rate in each margin: anterior and posterior surfaces of the pancreatic head; superior mesenteric/portal vein groove; superior mesenteric artery margin; transection pancreatic and bile duct margins, and its difference between the two arms compared. Finally, the impact of the margin status on survival was considered for each margin and type of periampullary tumours.

Calculation of the sample size was based on the literature assumption that the overall incidence rate expected of R1 ranged from 10 to 76% while it increased to 81-85% when a standardised pathological technique and margination with multicolour inking, as described in arm A, was performed. To detect a difference in R1 rate between these values with a 5% alpha-error and a 80% beta-error at a two-sided 0.05 significance level, a sample size of 18 patients was required for each group. In relation to the fact that the patients were often randomised without a preoperative biopsy, and that following current literature the 5-13% of the presumed malignancies were benign, it was decided to randomise 25 patients in order to avoid a sample size smaller than expected. The sample size calculation was carried out using PS Power and Sample Size Calculation software (Department of Biostatistics; Vanderbilt University; Nashville, TN, USA).

Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer

Multicolour Versus Monocolour Inking Specimens After Pancreaticoduodenectomy for Periampullary Cancer: a Single Center Prospective Randomised Clinical Trial.

Microscopic margin involvement (R1) was defined as a distance of the tumour from the resection margin of ≤1 mm.

Disease Free Survival and Overall Survival of the participants are measured using Kaplan-Meier curves.

Disease Free Survival and Overall Survival of the participants are measured using Kaplan-Meier curves and divided in subgroups related to their margin status (R0 versus R1).

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Associate Professor of Surgery at University of Bologna

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

ctDNA positivity in pretreatment and posttreatment plasma samples was defined by accessing the presence of one or more mutations identified in match tumor samples. A mutation was considered present when at least one consensus read contained the mutation and passed the local polishing pipeline. The MRD positive cohort was randomly divided into two groups, one group for interventional treatment and the other group for observation.

ctDNA negative in pretreatment and posttreatment plasma samples was defined by accessing the presence of no mutation identified in match tumor samples. According to the clinical prognostic characteristics of the MRD negative group, the clinician decides to observe or treat.

Patients with stage IB-IIA NSCLC after curative surgery were treated with adjuvant chemotherapy. The blood samples of the patients before and after adjuvant chemotherapy will be collected to examine the MRD status

Adjuvants, Pharmaceutic

Yunfeng Ni

Tao Jiang, MD

Yunfeng Ni, MD

Tao Jiang

This clinical trial aims to explore the minimal residual disease (MRD) status of early NSCLC after curative surgery and the clinical outcomes of adjuvant chemotherapy. Next-generation sequencing technique will be used to examine the circulating tumor DNA (ctDNA) from MRD of 150 postoperative patients with stage IB-IIA NSCLC who received adjuvant chemotherapy.

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and breast cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative NSCLC remain inadequate.

Circulating tumor DNA (ctDNA), a type of cell-free DNA, refers to the DNA fragments that are derived from tumor cells and circulate in the blood. Recently, next-generation sequencing (NGS) was successfully applied to monitor NPM1, RUNX1 and FLT3 mutations in multiple myeloma. Thus, NGS technique is a promising tool for sensitive MRD monitoring, which provides the ctDNA profiling from MRD, and then provides future decision-making treatment for postoperative NSCLC patients. Thus, this clinical study aims to monitor the ctDNA status of MRD, and to explore the clinical value of MRD monitoring in decision-making adjuvant therapy for patients with stage IB-IIA NSCLC after curative surgery.

A total of 150 patients with primary curable stage IB-IIA NSCLC will be recruited in this clinical trial. The following samples will be collected from each patient including 1) preoperative blood samples; 2) surgical tissue samples; 3) blood samples 3-7 days after surgery; 4) blood samples every 3-6 month during adjuvant chemotherapy; and 5) white blood control samples. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, PS score, etc. NGS will be used to analyze the whole exons of potential driver genes to obtain the MRD status. Statistical analyses will be performed to analyze the survival outcomes of MRD-positive and MRD-negative group and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative NSCLC.

Circular DNA from the blood samples of NSCLC patients before and after adjuvant chemotherapy were collected and examined by NGS

Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC

Utility of ctDNA In Predicting Whether Giving Adjuvant Chemotherapy In Patients With Stage IB-IIA Resected Non-small Cell Lung Cancer: A Prospective Cohort Study

DFS defined as the time from randomization to occurrence of any of the following events, whichever occurs first:

Locoregional recurrence or distant metastases as determined by an independent central radiology assessment.

Occurrence of the second primary (same or other) cancer as determined by an independent central radiology assessment.

Death from any cause. Loss to follow-up is censored.

Change of Circulating tumor DNA (ctDNA) status (every 3 months)

Occurrence of treatment emergent adverse event (TEAE)

Occurrence of dose reduction and discontinuation of IMP due to a TEAE

Follow-up of the patients will be conducted to analyze 3-year and 5-year overall survival

Tang-Du Hospital

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Dermatologic Agents

Analgesics

Tretinoin

Molgramostim

Sargramostim

Immunomodulating Agents

Isotretinoin

Interleukin-2

Dinutuximab

Immunologic Factors

Analgesics, Non-Narcotic

Dinutuximab will be administered at 17.5 mg/m2/day for 4 days up to 5 courses. Each dose should be infused IV over approximately 10 hours.

Immunotherapy (sargramostim + isotretinoin + interleukin2) Sargramostim will be administered at 250 micrograms/m2/d by subcutaneous (SC) injection daily from Day 0 through 13 (daily with the infusion of Dinutuximab and for 3 days before and 7 days afterward).

Isotretinoin (13-cis-retinoic acid, or RA) (160mg/m2/day or 5.33mg/kg/day if \< 12kg) PO divided into 2 doses daily x 14 days.

Interleukin-2 (IL-2) 3 MIU/m2/day will be given by continuous infusion for 4 days during the first week of each course 2 and 4 given on Days 0 - 3

Patients will receive 5 courses of Dinutuximab + GM-CSF + IL2 at intervals of 28 days for all courses. In addition, all patients will receive isotretinoin (13-cis-retinoic acid, or RA) at 160 mg/m2/dose twice a day for 14 days every 28 days, for 6 courses.

Patients come off study if progressive disease develops at any time after cycle 1 or life-threatening grade 4 toxicity occurs clearly attributable to Immunotherapy.

Dinutuximab. Immunotherapy

Jaume Mora, MD

The purpose of this study is to evaluate safety of the triple COG schema with the monoclonal antibody Dinutuximab + cytokines (GM-CSF and IL2) and isotretinoin (13-cis-retinoic acid, or RA) in patients with high-risk neuroblastoma.

Assess toxicity and safety of subcutaneous GM-CSF and iv IL-2 in enhancing Dinutuximab-mediated ablation of Bone Marrow (BM) disease in patients with high-risk neuroblastoma who have achieved a Complete Response or Very Good Partial Response of the macroscopic disease in the investigators institution.

Assess response of minimal residual disease (MRD) of the anti-GD2 monoclonal antibody Dinutuximab combined with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-2 in patients with high-risk neuroblastoma (NB). More precisely, to apply real-time quantitative RT-PCR to test the hypothesis that minimal residual disease content of BM after the first treatments with dinutuximab/GM-CSF has significant prognostic impact on relapse-free survival.

Safety Study of Dinutuximab Combined With Immunotherapy to Treat Neuroblastoma

Phase II Single Arm Study to Assess Dinutuximab (Ch 14.18) Combined With the Cytokines Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) and IL-2 in Patients With High-risk Neuroblastoma Not Eligible to Other Immunotherapy Trials

Type, incidence, severity, timing, seriousness, and relatedness; of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.

Rate of BM response for patients with detectable minimal residual disease in the BM after the first treatments with Dinutuximab/GM-CSF and relation with relapse-free survival.

Fundació Sant Joan de Déu

Neoplasm Metastasis

Recurrence

Pain

Neoplasm Recurrence, Local

Neoplasms, Second Primary

Disease Attributes

Depending on the modified Mizumoto Score (0-4 points or 5-9 points) patients will be treated with 10 fractions of 4.85Gy in involved parts of the vertebra and 3Gy in not-involved parts using a simultaneous integrated boost or with 5 fractions of 7Gy in involved parts of the vertebra and 4Gy in not-involved parts using a simultaneous integrated boost, respectively.

Fractionated radiosurgery using intensity-modulated treatment planning and volumetric image-guided treatment delivery

Radiosurgery

Matthias Guckenberger, MD

It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this II trial.

The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study.

1. A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety.
2. Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment.
3. Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept.

Evaluation of the single intervention - dose-intensified SBRT

Fractionated Radiosurgery for Painful Spinal Metastases

Dose-intensified Image-Guided Fractionated Radiosurgery for Spinal Metastases (DOSIS)

Decrease in pain by ≥2 points at the treated vertebral site on the 0 (no pain) to 10 (the severest pain) Visual Analogue Scale without analgesic increase

At the treated vertebral levels assessed with MRI

At the treated vertebral levels assessed with CT imaging

Measured with the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems) EuroQol 5-Dimension Questionnaire (EQ-5D) questionnaire

Measured with the EuroQol Visual Analog Scale from 0 ("the worst health you can imagine") to 100 (the best health you can imagine")

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer	NCT02900950	Stage, Pancreat... Neoplasm, Resid... Pancreatic Neop... Periampullary C...	Multicolour ink... Monocolour inki...	18 Years - 80 Years	IRCCS Azienda Ospedaliero-Universitaria di Bologna
Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer	NCT02900950	Stage, Pancreat... Neoplasm, Resid... Pancreatic Neop... Periampullary C...	Multicolour ink... Monocolour inki...	18 Years - 80 Years	IRCCS Azienda Ospedaliero-Universitaria di Bologna
Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC	NCT05167604	Carcinoma, Non-... Next-Generation... Chemotherapy, A... Neoplasm, Resid... Circulating Tum...	Adjuvants, Phar...	18 Years - 70 Years	Tang-Du Hospital
Safety Study of Dinutuximab Combined With Immunotherapy to Treat Neuroblastoma	NCT02169609	Neuroblastoma Neoplasm, Resid... Effects of Immu...	Dinutuximab. Im...	-	Fundació Sant Joan de Déu
Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC	NCT05167604	Carcinoma, Non-... Next-Generation... Chemotherapy, A... Neoplasm, Resid... Circulating Tum...	Adjuvants, Phar...	18 Years - 70 Years	Tang-Du Hospital
Fractionated Radiosurgery for Painful Spinal Metastases	NCT01594892	Neoplasm Metast... Neoplastic Proc... Neoplasm Recurr... Neoplasm, Resid... Pain	Radiosurgery	19 Years -	Wuerzburg University Hospital
Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer	NCT02900950	Stage, Pancreat... Neoplasm, Resid... Pancreatic Neop... Periampullary C...	Multicolour ink... Monocolour inki...	18 Years - 80 Years	IRCCS Azienda Ospedaliero-Universitaria di Bologna

Spots Global Cancer Trial Database for neoplasm, residual