A Post-treatment Program to Identify and Manage Complications Related to Oncology or Hematology Treatments in Cancer Survivors.

Study Overview
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Brief Summary
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INTRODUCTION: Approximately 44% of cancer survivors experience a deteriorated quality of life 5 years after diagnosis due to late onset of complications related to cancer treatments. The objective of the study is to evaluate the incidence rates of treatment-related complications, identify sub-clinical abnormalities and risk factors in patients participating in the PASCA post-treatment program. METHOD: PASCA is a single-center, interventional cohort study of adult patients who received at least chemotherapy and with a complete remission to a testicular germ cell tumor, primary non-metastatic invasive breast carcinoma, high-grade soft tissue sarcoma, osteosarcoma, Ewing's sarcoma, acute myeloid leukemia, Hodgkin's or aggressive non-Hodgkin's lymphoma. Four assessment visits will be scheduled at 1 month (T1), 6 months (T2), 24 months (T3) and 60 months (T4) after completion of treatment. During these visits, 22 complications will be screened and follow-up care will be systematically offered to the health professional concerned by the complication in case of a positive result. The screening will contain the following elements: screening self-questionnaires, quality of life questionnaire, 12 biological parameters, a urinalysis evaluating hematuria, proteinuria, and leukocyturia, a spirometry, an electrocardiogram, 5 tests evaluating physical condition, vital signs and the perimetric measurement between both arms. DISCUSSION: This systematic screening could highlight a number of complications occurring after cancer treatments. Sub-clinical abnormalities and new risk factors could also be identified. This new organization of care could improve the quality of life of adult cancer survivors.

Official Title
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Study of Complications Related to Treatments in Adults Aged 18 to 65 Years Old Responding to a First Treatment in Oncology or Onco-hematology and Participating in the PASCA (PArcours de Santé au Cours du CAncer) Post-treatment Program.

Conditions
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Non Hodgkin Lymphoma, Late Effects, Testicular Germ Cell Tumor Mixed, Non-Metastatic Breast Carcinoma, Soft Tissue Sarcoma, Adult, Stage IIC, Osteosarcoma, Ewing's Sarcoma, Acute Myeloid Leukemia, Hodgkin Disease

Intervention / Treatment
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* Other: PASCA intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old and ≤ 65 years old. Follow-up at the Léon Bérard center Treated by chemotherapy for one of the following pathologies, and confirmed by the reference diagnostic technique : acute myeloid leukemia; Hodgkin's lymphoma; aggressive non-Hodgkin's lymphoma; primary non-metastatic invasive breast carcinoma; testicular germ cell tumor treated with at least 3 courses of BEP (bleomycin, etoposide, cisplatin), 4 courses of EP (etoposide, cisplatin) or 4 courses of VIP (etoposide, ifosfamide, cisplatin) received; high-grade soft tissue sarcoma, osteosarcoma or Ewing's sarcoma. As a complete response at the end of treatment consultation. If end-of-treatment evaluation is not available at the time of inclusion: as an assumed complete response in the opinion of the investigator based on the previous assessment of response. Whose capacity to practice an adapted physical activity will have been certified by a medical certificate issued by the investigating physician, the general practitioner or the referring physician. Able to understand, read and write French. Available and willing to participate in the project throughout the duration of the study. Living in the Auvergne-Rhône-Alpes region or in the department of Saône-et-Loire Affiliated with a health insurance plan. Having declared an attending physician. Having signed and dated the informed consent. Exclusion Criteria: With a history of malignancy other than basal cell skin cancer. Cannot be followed for medical, social, family, geographical or psychological reasons for the duration of the study. Participating in other studies that could impact on the evaluation of the judgement criteria. Deprived of liberty by judicial or administrative decision.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: All patients in the study will benefit from the PASCA post-treatment program with 4 visits : at 1 month (T1), 6 month (T2), 24 month (T3) and 60 month (T4) after the end of treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PASCA intervention<br> | Other: PASCA intervention<br>* At each study visit (T1 = 1 month, T2 = 6 months, T3 = 24 months, T4 = 60 months), an exhaustive screening of complications as well as associated sub-clinical abnormalities and risk factors previously identified as such in the literature, will be conducted. Management of complications consists of referring the patient to a healthcare professional belonging to the PASCA network based on the test results. Referral is defined by referring to pre-established decision trees. It is made to a specialist physician, a health professional from the paramedical field or the patient's general practitioner who confirms the diagnosis if necessary and initiates the patient's care and follow-up. These patients also receive their usual follow-up in the context of their tumor pathology in oncology and onco-hematology.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of social precariousness | Diagnosed by a social worker | Month 1 | 
| Change from Baseline return to work issues incidence at 60 months | Diagnosed by a social worker | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline cognitive problems incidence at 60 months | Diagnosed by a neurologist | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline anxiety crises incidence at 60 months | Diagnosed by a psychologist or psychiatrist | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline depressive events incidence at 60 months | Questionnaire HADS-D (Hospital Anxiety and Depression scale) | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline chronic fatigue incidence at 60 months | Questionnaire MFI-20 (Multidimensional Fatigue Inventory) | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline physical deconditioning incidence at 60 months | A value below the lower limit on at least two of the following physical tests Six-Minute Walk Test (6MWT) (meters) Hand Grip Strength Test (Kg) Five Times Sit to Stand Test (number) Flamingo Test (sec) | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline overweight/obesity incidence at 60 months | BMI Waist circumference | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline chronic pain incidence at 60 months | Duration of pain Questionnaire DN4 (Douleur Neuropathique en 4 questions) | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline dermatological disorders incidence at 60 months | Common Terminology Criteria for Adverse Events (CTCAE) v5 | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline gastrointestinal disorders incidence at 60 months | Common Terminology Criteria for Adverse Events (CTCAE) v5 | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline sexual disorders incidence at 60 months | Questionnaire Sexualité VICAN5 | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline hypogonadism incidence at 60 months | Presence of clinical signs as defined by the International Society for Sexual Medicine A value below the lower limit on at least one of the following blood assay: level of total testosterone level of bioavailable testosterone | Month 1, Month 6, Month 24, Month 60 | 
| Change from 24 months premature ovarian failure incidence at 60 months | level of Follicle stimulating hormone level of estradiol | Month 24, Month 60 | 
| Change from Baseline osteoporosis incidence at 60 months | T-score evaluated by osteodensitometry, on the lumbar spine and upper end of the femur | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline chronic kidney failure incidence at 60 months | Diagnosed on the basis of 2 blood tests within 3 months using the same technique showing a decrease in GFR to < 60ml/min/1.73m2, estimated from creatinine levels using the CKD-EPI equation (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009), albuminuria or proteinuria positive, hematuria, leukocyturia > 10/mm3, or morphological abnormality on renal ultrasound. | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline heart failure incidence at 60 months | Diagnosed by a cardiologist with an echocardiography performing the Left Ventricular Ejection Fraction (LVEF) estimate | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline coronary heart disease incidence at 60 months | Diagnosed by a cardiologist conducting at least an interrogation with clinical examination, an estimation of pre-test probability of coronary artery disease | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline respiratory failure incidence at 60 months | Forced Vital Capacity Forced expiratory volume in 1 second Vital capacity Tiffeneau ratio Peak expiratory flow Total lung capacity Diffusing Capacity Of The Lungs For Carbon Monoxide | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline hypothyroidism incidence at 60 months | level of thyroid-stimulating hormone level of total thyroxine | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline lymphedema incidence at 60 months | Diagnosed by a vascular physician with a perimetric measurement of arms and forearms | Month 1, Month 6, Month 24, Month 60 | 
| Change from Baseline second primary cancers incidence at 60 months | Pathology report recorded in the patient file. | Month 1, Month 6, Month 24, Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the PASCA program: referrals made through the network | Number of referrals made through the network (attending physicians, specialist physicians, supportive care services or other health professionals) | Month 6, Month 24, Month 60 | 
| Evaluate the PASCA program: time between patient referral and completion of the first consultation | Average time (days) between patient referral and completion of the first consultation | Month 6, Month 24, Month 60 | 
| Evaluate the PASCA program: patient characteristics | Comorbidities at diagnosis Tumor classification cytogenetics mutations types and doses of each cancer treatments ratio of the number of patients included / number of eligible patients | Month 1, Month 6, Month 24, Month 60 | 
| Evaluation of the impact of program adherence on the evolution of the number of complications detected over time | Measurement of the association between program adherence rate and the number of complications detected over time | Month 6, Month 24, Month 60 | 
| Evaluation of the impact of program adherence on quality of life. | Measurement of the association between program adherence rate and the overall score on the secondary dimensions of quality of life. | Month 6, Month 24, Month 60 | 
| Description of the PASCA network : characteristics of health professionals sensitive to the post-treatment issues. | number of health professionals affiliated with the network type of health professionals affiliated with the network distribution over the Auvergne-Rhône-Alpes region according to medical speciality and department | Month 6, Month 24, Month 60 | 
| Identification of risk factors associated with complications occurring during follow-up. | Measurement of the association between suspected risk factors and the occurrence of a type of complication, during the duration of follow-up. | Month 1, Month 6, Month 24, Month 60 | 
| Description of the Global Longitudinal Strain | Evolution of the Global Longitudinal Strain in absolute value, relative to a later value | Month 6, Month 24, Month 60 | 
| Description of the Left Ventricular Ejection Fraction | Evolution of the Left Ventricular Ejection Fraction relative to a later value | Month 6, Month 24, Month 60 | 
| Description of the troponin I level | Evolution of the troponin I level relative to a later value | Month 6, Month 24, Month 60 | 
| Description of the Glomerular Filtration Rate | Evolution of the Glomerular Filtration Rate estimated by the CKD-EPI equation relative to a later value | Month 6, Month 24, Month 60 | 
| Description of spirometry values | Evolution of spirometry values relative to later values : Forced Vital Capacity Forced expiratory volume in 1 second Vital capacity Tiffeneau ratio Peak expiratory flow | Month 6, Month 24, Month 60 | 
| Incidence of diabetes mellitus | Level of fasting blood glucose | Month 6, Month 24, Month 60 | 
| Incidence of untreated high blood pressure | Measure of systolic blood pressure | Month 6, Month 24, Month 60 | 
| Incidence of hypertriglyceridemia | Level of triglyceridemia | Month 6, Month 24, Month 60 | 
| Incidence of hyper-LDL-cholesterolemia | Level of LDL-cholesterolemia | Month 6, Month 24, Month 60 | 
| Incidence of low level of physical activity | Questionnaire Godin-Shephard Leisure-Time Physical Activity | Month 6, Month 24, Month 60 | 
| Incidence of insufficiency / deficiency of 25(OH) vitamin D (D2+D3) | Level of 25(OH) vitamin D (D2+D3) | Month 6, Month 24, Month 60 | 
| Description of carcinogenic products consumption (tobacco, alcohol, cannabis) | Number of packages years Questionnaire DETA-Cage | Month 1, Month 6, Month 24, Month 60 | 
| Evaluation of the Progression-free survival | Evaluation of the Progression-free survival | Month 6, Month 24, Month 60 | 
| Evaluation of the Survival without an increase in the number of complications, among those studied | Evaluation of the Survival without an increase in the number of complications, among those studied | Month 6, Month 24, Month 60 | 
| Evaluation of the event-free survival | Evaluation of the event-free survival | Month 6, Month 24, Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Late Effects, Survivors, Adults, Screening, Tertiary prevention, Testicular Germ Cell Tumor Mixed, Non-Metastatic Breast Carcinoma, Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, Acute Myeloid Leukemia, Hodgkin Disease, Non Hodgkin Lymphoma