Quale follow-up per i pazienti anziani con linfoma? Francesco Merli Ematologia Arcispedale S.Maria Nuova-IRCCS Reggio Emilia

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1 Quale follow-up per i pazienti anziani con linfoma? Francesco Merli Ematologia Arcispedale S.Maria Nuova-IRCCS Reggio Emilia

2 Conflitto di interessi Il sottoscritto Francesco Merli ai sensi dell art. 3.3 sul Conflitto di Interessi, pag. 17 del Reg. Applicativo dell Accordo Stato - Regione del 5 novembre 2009 dichiara che negli ultimi due anni ha avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario: Roche, Takeda, Celgene, Gilead, Pfizer, Mundipharma, Janssen

3 Cancer, July For older patients with NHL survival has, in general, been increasing at least as fast as for younger patients The age-related disparity in survival has actually been decreasing NHL

4 Follow up definition Follow-up cancer care involves regular medical checkups that include a review of a patient s medical history and a physical exam. Follow-up care is important because it helps to identify changes in health. The purpose of follow-up care is to check for recurrence (the return of cancer in the primary site) or metastasis (the spread of cancer to another part of the body). Follow-up care visits are also important to help in the prevention or early detection of other types of cancer, address ongoing problems due to cancer or its treatment

5 Early and late FU Short -term FU relapse early disease detection Long-term FU sequelae cancer survivorship

6 Which FU

7 Which FU Advanced stage HL patients in complete remission after induction therapy (N = 300) Picardi M. et al. Radiology 272 (1): ; 2014

8 Which FU Primary end-point: equivalence in sensitivity between FDG-PET/CT and US/CXR Secondary end points: PPV; exposure to ionizing radiation; costs Picardi M. et al. Radiology 2014

9 Which FU No difference between the PET/CT and UC/CXR regarding curves for the time from baseline untill recurrence detection. Relapse Symptoms No symptoms PET/CT (40) US/CXR (40) Picardi M. et al. Radiology 2014

10 Maurer MJ et al, JCO 2014 Patients with DLBCL who are event-free at 2 yrs have an identical OS to that of the general population, emphasising the need to only specifically monitor the disease in this early period Cause of death in patients achieving EFS 24 months since diagnosis

11 DLCL follow up in clinical guidelines History and PE Radiological evauation Blood exam PET scan NCCN mos for 5 yrs then annually CT scan no more often than every 6 mo for 2 y 3-6 mos for 5 yrs then annually Not indicated ESMO mos 1 year 6 mos 2nd 3 year then annually CT scan common 6,12,24 months but no definitive evidence 3,6,12,24 months than if needed Not indicated AIOM mos 1-2 year 6 mos 3-5 year then annually CT 6,12, 24 mos 3 mos 1-2 year 6 mos 3r- 5 year then annually Not indicated Lugano mos 1-2 year 6 mos 3-5 year then annually Only in clinical trial with time-dependent endpoint 3 mos 1-2 year 6 mos 3-5 year then annually Not indicated SIE mos 1-2 year 6 mos 3-5 year then annually CT 6,12, 24 mos, then annually until year mos 6 mos 3-5 year then annually --- THERE ARE FEW DATA TO SUPPORT SPECIFIC RECOMMENDATIONS: USUALLY THEY REPRESENT THE RANGE OF CLINICAL PRACTICE

12 Blood, 2017 No retrospective or prospective study identified a survival advantage associated with the use of surveillance imaging for patients with DLBCL or HL who achieved remission after first-line therapy.

13 Blood, 2017 Imaging also has disadvantages: a meaningful fraction of patients experience false-positive scan results (additional anxiety and medical interventions) Surveillance imaging produces additional radiation exposure: the risk of additional cancers and cancer related death attributable to this exposure appears to be slight for most adults Novel approaches to disease surveillance are under development: circulating tumor DNA: non invasive, no radiation, ability to detect relapse early Prospective studies are needed to determine whether surveillance imaging might provide benefit in HIGHLY selected populations (DLBCL high risk / HL with positive interim PET.)

14 Blood, 2017 RECCOMENDATIONS patients with HL and DLBCL who achieve CR: should not receive routine surveillance imaging GRADE 1B (strong recommendation with decent evidence) high risk patients (ex: DLBCL IPI of 3-5) : it is reasonable to consider scans on an individual basis (after discussion of the risks and benefits of surveillance imaging) early detection of relapse is not currently known to improve survival GRADE 2C (weak recommendation with fair evidence) In these highly selected cases, surveillance should be limited to the first 2 years after induction therapy as the risk of relapse declines significantly at that time point and routine imaging is likely no longer appropriate.

15 Follow-up: imaging or clinical? 258 relapsed patients: 173 DLBCL 43 HL 42 PTCL American Journal of Hematology 2014

16 Follow up: imaging or clinical? Physical examination: Every 4 months in first two years Every 6 months in next three years Yearly till 10 years Imaging surveillance: Every 6 months for first two years Annually 3-5 year Relapse detection: 64% PE or patients reported symptoms 26% Routine imaging detection 60% Relapses within the first year of follow-up El Galaly,AJH 2014

17 Imaging or clinical FU? Bi- annual CT during the first 2 years Imaging detected relapse as a proportion of all CR- CRu - 3% in DLBCL - 2% HL - 4% PTCL routine scans in NON-RELAPSING patients Clinical symptoms remain the leading factor in diagnosis recurrent lymphoma in the era of modern imaging Restricting the use of surveillance imaging to patients at high risk of relapse could tip the balance towards a better risk/benefit ratio El Galaly,AJH 2014

18 Series: 680 DLBCL cases from MER Iowa / Mayo Clinic Independent cohort :222 DLBCL cases from Leon Berard/Lyon 680 Objectives: how many relapses detected outside/inside the time frame of scheduled visits

19 Utility of routine surveillance imaging 680 pts MAYO 552 CR 9/552 : 1.6% (Lyon 1.8%) 112 relapse 67 before scheduled visit (63 DLCL) 37 scheduled visit (22 DLCL) 24 clinical features of relapse 13 asymptomatic 4 low grade 9 DLCL Thompson, JCO 2014

20 Utility of routine surveillance imaging 88-91% pts showed at least one clinical No OS difference between relpase detected inside or outside scheduled FU visits Thompson, JCO 2014

21 Early and late FU Short -term FU relapse early disease detection Long-term FU sequelae cancer survivorship

22 Who is a cancer survivor? AUTORE DEFINIZIONE MULLAN, 1985 CHI HA UNA DIAGNOSI DI TUMORE AM CANC SOC, 2002 VIVO A 5 ANNI DALLA DIAGNOSI DI TUMORE ROWLAND, 2006 DALLA DIAGNOSI AL DECESSO STAM, 2006 TRATTAMENTI COMPLETATI DA 5 ANNI KNOBF, 2007 LIBERO DA MALATTIA DOPO I TRATTAMENTI FEUERSTEIN, 2007 CHI HA TERMINATO I TRATTAMENTI

23 Hodgkin lymphoma: the price of success Armitage JO. N Engl J Med 2010;363: Ng A, Blood 2014; 124

24 FOLLOW-UP DEI LINFOMI: QUALE MODELLO?

25 Cancer survivors : the size of the matter Cancer Survivors Italy ,5 M ,75 M

26 Cancer survivors in US Miller KD, Ca Cancer J Clin 2016

27 Screening for cancer survivors Many survivors may be so focused on recurrence that they risk neglecting other aspects of their health long-term or late effects from treatment As more time passes from the conclusion of active treatment, the risk for recurrence decreases and the need to focus on other aspects of survivor health should move to the forefront Obesity, inactivity, poor dietary quality, and continued smoking after cancer diagnosis linked to increased risk of cancer recurrence and mortality in individuals with common cancers

28 Long term follow up in the elderly: screening for second cancers? BREAST CANCER Women with mediastinal irradiation Start screening 8 years after mediastinal RT RM if <30 years Mammography if >50 yrs? years Mammography if adeguate breast parenchyma density Otherwise RM + mammography LUNG CANCER Smokers males with previous RT CHEST CT scan starting 6-15 years after treatment Counseling for smoking cessation COLORECTAL CANCER Previous abdominal RT > 25 Gy Start screening 15 before general population 35 years

29 Long term FU : screening for late sequelae CARDIOVASCULAR LOGIC (RT- ANTHRA) ECG baseline Echo or MUGA baseline, then periodically based on RT, anthra and age Lipid profile yearly Carotid artery yeras RESPIRATORY (BLEOMYCIN) Spirometry / DLCO at baseline, then based on results Hypothyroidism (neck- RT) TSH yearly

30 Spectrum of potential side effect Depression Hot flashes/night sweats Weight gain Cardiovascular effects Cognitive dysfunction Sexual dysfunction Radiation therapy Chemotherapy Monoclonal antibody Hormonal therapy Chronic fatigue Genitourinary symptoms Other 2nd-malignancy (ie, endometrial cancer) Osteoporosis/ bone fractures Arthralgia/joint symptoms

31 FOLLOW-UP DEI LINFOMI: QUALE MODELLO? Recommendations for Initial Evaluation, Staging, and Response Assessment of HL and NHL: The Lugano Classification B. Cheson et al, 2014 STUDIES DO NOT SUPPORT ROUTINE SURVEILLANCE SCANS FOLLOW-UP SCANS SHOULD BE PROMPTED BY CLINICAL INDICATIONS IN CLINICAL PRACTICE/CLINICAL TRIALS, ATTEMPTS SHOULD BE MADE TO LIMIT NUMBER OF SCANS TO WHICH A PATIENT IS EXPOSED

32 Conclusions Short -term FU relapse early disease detection Decrease intensity Decrease imaging surveillance Consider if active second line exist LESS IS BETTER Long-term FU sequelae cancer survivorship Plan late effect screening based on specific treatment Plan long-term f.u.related to comorbidities (elderly!!!) Never stop? Elderly? MORE IS BETTER

33 Follow up nei linfomi : quesiti aperti Q. CHI DEVE FARE IL FOLLOW-UP DURANTE TERAPIA? A. EMATOLOGO O ONCOLOGO O RADIOTERAPISTA Q. E GIUSTIFICATO UN FOLLOW-UP INTENSIVO? A. ASSOLUTAMENTE NO! Q. PER QUANTO TEMPO IL FOLLOW-UP SPECIALISTICO? A. 3-5 ANNI Q. E DOPO 3-5 ANNI QUALE FOLLOW-UP? A. SECOND CANCER / LATE TOXICITY

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