Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) once a week over 28 days

Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) other 9 days.

Minimize radiation doses to surrounding area

Intensity modulated radiation therapy

Volumetric modulated arc therapy

Follow target by the use of fiducial markers and ERB

Image guided radiation therapy

Thomas Zilli, Dr

RATIONALE: It is not yet known whether extreme hypofractionation is equally safe and effective than standard radiation therapy in treating prostate cancer.

PURPOSE: This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated Radiation Therapy for prostate cancer.

This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated RT for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules: either over 9 days (study A), or over 28 days once-a-week, the same week-day (study B).

The total dose and fractionation schedules have been chosen based on the assumption of their isoeffectivity regarding potential late rectal effects to be expected with a maximum equivalent dose of 74 Gy in 2 Gy fractions and assuming an alpha/beta = 3 Gy for the rectum.

In both arms, the prescribed dose per fraction to the urethra and the surrounding transitional zone will be dropped from 7.25 Gy to 6.5 Gy with a simultaneous integrated boost (SIB) technique. A dose of 5 x 6.5 Gy is equivalent to 31 x 2 Gy assuming an alpha/beta = 3 Gy for the urethra and equivalent to 37 x 2 Gy assuming an alpha/beta = 1.5 Gy for microscopic tumour foci in the transitional zone surrounding the urethra. The two treatment regimens chosen will each be the object of a separate phase I-II study covered by the same protocol and performed in parallel by the participating centres. Randomised assignment to either of the two studies will be introduced to avoid selection bias in treatment assignment within each centre.

OBJECTIVES:

Primary

* To determine the risk of urinary, rectal and sexual acute and late toxicities rates in patients receiving two different time schedules of extreme hypofractionated radiation therapy

  • Secondary
* To determine the Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25) in patients receiving two different time schedules of extreme hypofractionated radiation therapy
* To determine the rate of local failure
* To determine in the two study arms the biochemical disease-free survival bDFS rate
* To determine in the two study arms the metastases-free survival rate
* To determine in the two study arms the disease-specific survival rate

OUTLINE:

This is a multicenter study.

Patients undergo extreme hypofractionated radiation therapy for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules:

Experimental Arm A: Over 9 days. Experimental Arm B: Over 28 days once-a-week, the same week-day. All patients will be followed up for at least 18 months to contribute to the analysis of the main endpoints of the study. With reference to the secondary endpoints, follow-up will be extended to 10 years.

Stopping rule: In order to avoid exposure of patients to a treatment that may be unsafe, acute GI and GU toxicity will be continuously monitored with the purpose of assisting in the decision of possibly interrupt recruitment in case of an alarming frequency.To this purpose, the procedure of Ivanova et al., 2005 will be applied.

5 x 7.25 Gy delivery in 2 alternative time Schedule: over 9 days every other treatment or over 28 days once a week

Hypofractionated Radiation Therapy in Prostate Cancer

Stereotactic Body Radiation Therapy for cT1c - cT3a Prostate Cancer With a Low Risk of Nodal Metastases (≤ 20%, Roach Index): a Novalis Circle Phase II Prospective Randomized Trial

No plan to share participant data for now

Tolerance to treatment (urinary, rectal, sexual): Acute (up to 90 days) and late (up to 5 years) toxicity follow-up according to NCI CTCAE version 3.0

Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25)

Assessed by digital rectal examination (DRE). MRI or PET-CT with choline or acetate may be a confirmatory option. Biopsy confirmation is required for those patients with exclusive local failures and candidates for local salvage.

Outcomes 3 or 4 - investigations PET-CT choline

Alive/dead status, date and cause of death and prostate cancer disease status (outcomes 3/4 and 5).

Thomas Zilli

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Disease Progression

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Pretreatment lymphocyte to monocyte ratio in non-metastatic patients with renal cell

cancer and overall survival cancer specific survival cancer and recurrence-free survival cancer and disease-free survival lymphocyte to monocyte ratio in non-metastatic renal cancer and progression-free survival

prognosis

Garcia-Rojo

Dario Garcia-Rojo

PubMed, ScienceDirect, Cochrane Database of Systematic Reviews will be used to search for articles published from January 1965 to July 2019 using the key words "renal cancer", "lymphocyte to monocyte ratio" and "prognosis". No restrictions to date, language, or article type will be applied. Cohort or observational studies in patients with non-metastatic renal cell carcinoma histopathologically confirmed, with hazard ratios (HR) and corresponding 95% confidence intervals (CI) that assessed association between LMR and overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and disease-free survival (DFS) will be analyzed.

A systematic review of the literature will be carried out using Patient, Intervention, Comparison and Outcome method (PICO), with the aim of answering the following clinical question: "Is pretreatment under lymphocyte to monocyte ratio (LMR) a prognostic factor in non-metastatic renal cell carcinoma ? "

All analyzes will be based on previously published studies. For this reason, patient consent and ethical approval will not be required.

An exhaustive search will be conducted in PubMed, Science Direct and Cochrane Database of Systematic Reviews for eligible studies that explored the prognostic role of LMR in patients with localized renal tumors, who underwent to partial or radical nephrectomy from January 1965 to July 2019. The terms search will include: "monocyte lymphocyte ratio", "renal cancer", "prognosis".

Cohort studies or observational studies will be included, patients with localized renal tumors who underwent partial or radical nephrectomy, with histopathologically confirmed neoplasms, who had access to the full text and without language limitation.

Inclusion:

Any observational study (cross-sectional, case-control, longitudinal with cross-sectional data) will be included.

Patients with localized renal tumors who underwent partial or radical nephrectomy, with histopathologically confirmed neoplasms, who had access to the full text and without language limitation will be included.

Exclusion: Reviews, case reports, conference abstracts, letters, animal or cell studies.

Relevant articles will be identified in duplicate by two independent reviewers by first screening the titles and abstracts followed by the full text against inclusion and exclusion criteria. Any disagreement will be resolved by consensus with a third reviewer experienced in the renal cancer management.

The studies reflected the hazard ratio (HR) and corresponding 95% confidence intervals (CI), in which the overall survival (OS), specific cancer specific survival (CSS), recurrence-free survival (RFS), disease-free survival (DFS) and progression-free survival (PFP).

Information will be extracted for the first author, publication year, geographic location, study design, patient information (sample size, mean/median age, sex distribution, performance status), LMR, endpoint (OS, CSS, RFS, DFS, PFS), therapy, follow up duration, multivariate factors, hazard ratio (HR) and corresponding 95% confidence intervals (CIs), or exact P values. When univariate HR and multivariate HR were both reported, only the multivariate HR will be used.

OS is defined as the interval from the date of surgery in the primary tumor until death. CSS is defined as the interval from the date of surgery in the primary tumor to death for urological tumors. RFS is defined as the interval from the date of surgery in the primary tumor to local, regional or distant recurrence or death from any cause. DFS is defined as the interval from the date of surgery in the primary tumor to local, regional or distant recurrence. PFS is defined as the interval from the date of surgery in the primary tumor to the progression of the disease (including local recurrence or distant metastasis) or death.

The Newcastle-Ottawa Scale (NOS) will be used to assess the quality of studies. A maximum of 9 points can be given for each study in the categories of: selection of patients, comparability of the study groups, and assessment of outcomes. We will define high-quality studies with scores \>7.

If the necessary data are available, subgroup analyses will be performed to explore the potential sources of heterogeneity according to country, analysis type, tumor type, sample size and cut-off value.

Statistical study:

Data will be combined using random effect models. The Cochrane χ² (Cochrane Q) statistic and the I² test will be used to analyze heterogeneity.

Before calculating the combined results for all trials, statistical heterogeneity will be evaluated by using the I² statistic and p-value, which assessed the appropriateness of pooling the individual study results. The I² value provided an estimate of the amount of variance across studies because of heterogeneity rather than chance. I² values of 25%, 50%, and 75% corresponded to low, moderate, and high levels of heterogeneity, respectively. If p\> 0.05, the heterogeneity will be not substantial. Thus, a fixed-effect model will be used to calculate forest plots. If p \< 0.05, however, the heterogeneity will be considered substantial. Then a random effects models were used.

The publication bias will be graphically explored through funnel plot, and Duval and Tweedie's "trim-and-fill" test will be used to correct possible publication bias.

Statistical significance was defined as p less than 0.05.

Statistics will done using R 3.5.0 (R Core Team, 2018) and the meta (v4.1-5; Schwarzer, Guido, 2019) package.

Meta-analysis of the Prognostic Value of Lymphocyte to Monocyte Ratio (LMR) in Non-metastatic Renal Cell Carcinoma.

Prognostic Value of Pretreatment Lymphocyte-to-monocyte Ratio in Patients With in Non-metastatic Renal Cell Carcinoma: a Systematic Review and Meta-analysis

Preoperative Lymphocyte to Monocyte Ratio ( LMR) is a prognostic factor patients who underwent nephrectomy for non-metastatic renal cell carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypofractionated Radiation Therapy in Prostate Cancer	NCT01764646	Malignant Neopl... Local Disease	Intensity modul... Volumetric modu... Image guided ra...	18 Years - 85 Years	University Hospital, Geneva
Hypofractionated Radiation Therapy in Prostate Cancer	NCT01764646	Malignant Neopl... Local Disease	Intensity modul... Volumetric modu... Image guided ra...	18 Years - 85 Years	University Hospital, Geneva
Meta-analysis of the Prognostic Value of Lymphocyte to Monocyte Ratio (LMR) in Non-metastatic Renal Cell Carcinoma.	NCT04213664	Renal Cell Carc... Progression Lymphocyte Diso... Monocytosis Local Disease	prognosis	18 Years -	Corporacion Parc Tauli
Meta-analysis of the Prognostic Value of Lymphocyte to Monocyte Ratio (LMR) in Non-metastatic Renal Cell Carcinoma.	NCT04213664	Renal Cell Carc... Progression Lymphocyte Diso... Monocytosis Local Disease	prognosis	18 Years -	Corporacion Parc Tauli

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