1

Paolo MarchettiOncologia Medica

II Facoltà diMedicina e ChirurgiaSapienza

Università di RomaAzienda

Ospedaliera Sant’Andrea

Roma

La terapia di supporto

2

Paolo MarchettiOncologia Medica

II Facoltà diMedicina e ChirurgiaSapienza

Università di RomaAzienda

Ospedaliera Sant’Andrea

Roma

La simultaneous care!

3

Oggi…• La tutela della salute = prodotto

• L’assistenza sanitaria = servizio

• il malato = utente

• l’ospedale = azienda

• lo Stato, definisce, eroga, paga e controlla le prestazioni.

ma è corretto definire la salute come un prodotto o servizio e la persona malata come cliente o utente?

3

4

Significant unmet needs

• Significant unmet needs are those needs that patients identify as both important and unsatisfied.

• The range of unmet need, and the kinds of patients who are more likely to claim unmet need, should be carefully identified.

K. Soothill et al., Supportive Care in Cancer, 2001

5

Simultaneous care in oncology

Unmet needs in cancer patients

5

6

Significant unmet needs

• The NHS Cancer Plan [2000] has highlighted the need to streamline cancer services ‘around the needs of the patient’ and to provide ‘the right professional support and care as well as the best treatments’.

• However, the real question is whether the overall needs of cancer patients are actually being met.

K. Soothill et al., Supportive Care in Cancer, 2001

7

Number of unmet needs

K. Soothill et al., Supportive Care in Cancer, 2001

8

Significant need and unmet need Top 18 items

K. Soothill et al., Supportive Care in Cancer, 2001

9

Current State

Descriptions of primary orientation in cancer system:

tumour care

acute/episodic

institutionally based

professionally driven Current State

System of care frequently labeled as: fragmented

inaccessible

quality variation

disempowering

provider oriented

CANADIAN STRATEGYCANADIAN STRATEGYFOR CANCER CONTROLFOR CANCER CONTROL

—— REBALANCING FOCUS REBALANCING FOCUS ——

10

Ministero della SalutePIANO ONCOLOGICO NAZIONALE

2010/20123.0 Il percorso del malato oncologico nel SSN pag. 37 3.1 Integrazione del percorso diagnostico-terapeutico pag. 37

3.1.1 MMG - Associazioni 3.1.2 Assistenza ambulatoriale 3.1.3 L’ ospedale 3.1.4 Azioni programmatiche 3.2 La continuità assistenziale sul territorio pag. 40 3.2.1 Ottimizzazione dei percorsi di cura e organizzazione di rete 3.2.2 Strumenti informatici a supporto dell’assistenza oncologica: i Sistemi CUP 3.2.3 Il modello simultaneous care (presa in carico del malato oncologico) 3.2.4 Riabilitazione dei malati oncologici 3.2.5 Cure palliative 3.2.6 Sviluppo della terapia del dolore 3.2.7 Sviluppo della psico-oncologia 3.2.8 Integrazione con il no profit e il volontariato 3.2.9 Azioni programmatiche 3.3 Il paziente oncologico anziano pag. 48 3.3.1 Considerazioni generali 3.3.2 Ottimizzazione dei percorsi di cura per il paziente anziano oncologico 3.3.3 Integrazione/coordinamento dell’assistenza intra ed extraospedaliera al paziente anziano 3.3.4 Azioni programmatiche

11

WHAT IS PERSONALIZEDHEALTHCARE?

• Medical practices that are targeted to individuals based on their specific genetic code in order to provide a tailored approach.

• The goal of personalized health care is to improve health outcomes and the health care delivery system, as well as the quality of life of patients everywhere.

12

Every tumor develops a unique antigenic fingerprint.

Every Tumor is Unique!Mutations Are Random.

10-8 per bp per cell division cycle on 6 x 109 bp = thousands to millions of unique mutations

13

Every patient develops a unique individual fingerprint.

Every Patient is Unique!Problems Are Random.

thousands of unique problems!

14

Leaving the era of the “median results”, but targeting … what?

• Patient: – Genotype and polymorphisms:

• role of SNPs (CYP2D6)

• Tumor: refining the population target– Proliferation gene Index (PGI): the best ?– RE+/PG- population: does it mean

something?– EGFR: is or is not ?– Triple negative BC: time for separating ?

15

Tamoxifen activity is related to its metabolic pathway

Tamoxifen metabolites have different anti-estrogenic power.

80 variant alleles of cytocrome p450 2D6

Alleles 3,4 5 6 account for 99% of the variants

Catalyzes metabolism of many common drugs

Inhibited by flouxetina and paroxetina, frequently used by women assuming tamoxifen

16

Practical implication

• Very important remind: we deal not only with the tumor, but also with the host

• Similar observation with other anti-hormonal drugs (i.e. CYP19 and Letrozole, ASCO 2004)

• Confirmatory and prospective studies needed• In the meanwhile, pay attention to all drugs

you administer in combination with TAM, particularly new antidepressant– implication in some type of drug resistance?

17

Leaving the era of the “median results”, but targeting … what?

• Patient: – Genotype and polymorphisms:

• role of SNPs (CYP2D6)

• Tumor: refining the population target

18

Histologically they look like, but…

Pt 47 yrs, pre-menopausal

T 2.4 cm, N (-), G1 ER (±)/PR(+), HER-2 (-)

12/2003: QUARTFEC100 x 6 LHRH-Tam

Pt 39 yrs, pre-menopausal

T 2.2 cm, N (-), G1 ER (±)/PR(+), HER-2 (-)

09/2000: QUART FEC100 x 6 LHRH-Tam

Topoisomerase II By courtesy of S. Iacobelli, 2006

10/2004: Metastatic disease09/2005: NED

19

Cancer Biology

• Diversity of tumor subtypes: time for separating patients and treatments?

• Going inside to cancer biology can help clinicians?

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Targeting Dysregulated Pathways With Novel Agents

21

100%

90 %

80 %

70 %

60 %

50 %

40 %

30 %

20 %

10 %

0 %

Circulating Tumor Cells at First Follow-Up Predict Progression-Free Survival

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80

<5 CTC (n=114), ~7.0 months≥5 CTC (n=49), ~2.1 months

~7.0 months

Time from baseline (weeks)

First follow-up (3-4 wk), n=163, Logrank p < 0.001

Cristofanilli M et al. N Engl J Med 2004;351(8):781-91.

~2.1 months

Per

cen

t p

rob

abil

ity

of

pro

gre

ssio

n-f

ree

surv

ival

CTC = circulating tumor cells

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Challenges of cancer treatment

The key goals of cancer treatment remain to

• Cure patients

• Improve overall survival

• Improve quality of life

• Identify novel targets and therapeutics

• Provide more tailored, individualized treatment

23

24

25

Leaving the era of the “median results”, but targeting … what?

• Patient• Tumor

•The patient with a cancer!

26

How Accurate Is Clinician Reporting of Chemotherapy Adverse Effects?

J Clin Oncol. 2004; 22: 3485-3490.

38 65 77 65 70 17 30 6010080

60

40

20

0

Fatig

ue

Pain

Dys

pnea

Inso

mni

a

Ano

rexi

a

Nau

sea/

Vom

iting

Dia

rrhe

aC

onst

ipat

ion

Per

cen

tag

e

Physician identified Physician missed

Slamon D. SABCS 2005. General Session I.

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Percezione dei sintomi:un obiettivo comune?

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ESMO takes a stand on supportive and palliative care

• Make alleviation of pain and other symptoms a high

priority

• Medical oncologist must be expert with the evaluation

and management of pain and other symptoms

• Cancer center should provide supportive and

palliative care as part of the basic basket of services.

(Ann Oncol 14: 1335, 2003)

29

Bridging the Divide: Integrating Cancer-Directed Therapy and Palliative Care

• We must take symptom management a priority at diagnosis,

throughout treatment, during periods without treatment, and

finally, at the end of life

• We need all of these effort and more to traverse the divide

that now exists between palliative care and cancer-directed

therapy.

(JL Malin, JCO 22: 3438, 2004)

3030

“Doc, I’m tired…”

3131

Fatigue

Agreement and disagreement

between patients and clinicians.

E. Basch et al., Lancet Oncol 2006

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Survival According to the Underlying Cause of Cardiomyopathy

Felker GM, et al. N Engl J Med. 2000;342:1077-1084.

1.00

0.75

0.50

0.25

0.000 5 10 15

Years

Peripartum

Idiopathic

ischemic heart diseaseDue to

Due to HIV infection

Due to infiltrative myocardial disease

Due to doxorubicin therapy

1%

Pro

po

rtio

n o

f P

atie

nts

Su

rviv

ing

33

43.7% of Medical Oncologists used multiple symptoms tools and 37.9% used symptom specific tools;

58.9% used some instrument to assess pain.

More than a third of the respondents (35.5%) used patient-tailored protocols.

No statistical differences were found regarding region of residency, availability of consultants in pain therapy and/or palliative care, colleagues with main interest on palliative care, and beds dedicated to palliative care.

3434

35

3636

BreakThrough Cancer Pain (BTcP)

37

Prevalence of BTcP

• The prevalence of BTcP may differ due to the stage of the cancer and the methodology of the different studies, but it remains an important problem in cancer patients who are already receiving treatment for their pain.

• Up to 95% of patients with cancer suffer from BTcP.

Zeppetella G, Ribeiro MD. Pharmacotherapy of cancer-related episodic pain. Expert Opin Pharmacother 2003

38

Terapia dei sintomi

39

Nutrition assessment

Weight loss at the time of diagnosis has been associated with decreased survival and reduced response to treatment.

Dewys WD, Am J Med, 1980

Treatment of nutrition-related symptoms reverse weight loss in in 50-88% of cancer patients.

Ottery FD, Proc Am Soc Clin Oncol, 1998

Assessment with Patient-Generated Subjective Global Assessment (PG-SGA), anthropometric and laboratory data or Bioelectrical Impedance Analysis (BIA– unavailable in most ambulatory settings)

Sungurtekin H, Nutrition, 2004

Lukaski HC, Ann N Y Acad Sci, 1999

40

Cancer rehabilitation is the process that assists the cancer patients to obtain maximal physical, social,

psychological and vocational functioning within the limits created by the disease and its treatment

41

The rehabilitation approach to cancer treatment originates with National Cancer Act (NCA) of 1971

In 1972, the NCI sponsored the National Cancer Rehabilitation Planning Conference and developed training programs and research projects to identify 4 objectives in cancer rehabilitation:

Psychosocial support

Optimization of physical functioning

Vocational counselling

Optimization of social functioning

42

why do women fear breast cancer more than any other health risk?

One out of two women in the United States will die from heart disease or stroke.

Women also believe ovarian cancer is their biggest "cancer" threat when it is actually lung cancer that kills 70,000 women a year.

43

Breast Cancer Risk:Perception vs RealityNearly 90% of Women Overestimate Breast Cancer

Risk

• When asked to estimate the average lifetime chance of developing breast cancer, nine out of 10 women overestimated the risk.

• The risk was perceived three times higher than it actually was.

P. Ubel et al., Patient Education and Counseling, 2005

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Breast Cancer Risk:Perception vs RealityNearly 90% of Women Overestimate Breast Cancer

Risk

Estimating Risk• Roughly one in eight women will eventually develop

breast cancer. In other words, a woman has a 13% chance of developing breast cancer at some point during her life.

• Numbers don't give context: asking the patients to estimate their own risk can help put the actual risk in perspective.

• We shouldn't just throw numbers at patients without giving them some context for those numbers!

P. Ubel et al., Patient Education and Counseling, 2005

4545

One Size Doesn't Fit All!

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Comprendere ilPaziente!

• Quanto è grave la sua malattia?

• Quanto è curabile la sua malattia?

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The risk perception attitude (RPA) framework

• Four attitudinal groups based on their perceptions of risk and beliefs of personal efficacy.– Responsive (high risk, high efficacy)– Avoidance (high risk, low efficacy)– Proactive (low risk, high efficacy)– Indifference (low risk, low efficacy)

• These groups differ from each other in their self-protective motivations and behaviors.

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48 48

Comunicare in oncologiaCosa?

•Il tipo di trattamento•Gli effetti collaterali•Le risposte attese•La prognosi

49 49

… ma anche

• I risultati delle rivalutazioni clinico-strumentali– Assenza di tumore o non evidenza di

ripresa di malattia?– Angoscia per i prossimi controlli o falsa

tranquillità per i successivi 6/12 mesi?

50 50

… ma anche

• Variazioni nel tipo di farmaco usato– Paziente asintomatica, senza

progressione di malattia, preoccupata di eventuali nuovi effetti collaterali.

– Paziente sintomatica, preoccupata che il cambio di farmaco sia dovuto ad un fallimento della precedente terapia

51 51

Caso clinico

• Paziente di 70 anni, operata per un ca della mammella da 2 anni, in trattamento adiuvante (precauzionale) con tamoxifen.

• Sulla base dei risultati con gli IA, deve sostituire il tamoxifen con un IA.

• La Paziente non ha avuto alcun effetto collaterale con il tamoxifen.

• Informata dei possibili effetti collaterali degli IA, è spaventata.

• Rinuncerà ai benefici della nuova terapia?

52 52

l’informazione sulla diagnosi di tumore secondo le risposte dei caregiver

% (95% CI)SI 37 (34-40)NO, ma lo sapevano 29 (27-32)NO e non lo sapevano 26 (24-29)NO, non so se sapevano

7 (6-10)

Al paziente è stato detto che aveva un tumore?

M. Costantini et al., Ann Oncol, 2006

53 53

l’informazione sulla diagnosi di tumore secondo le risposte dei caregiver

M. Costantini et al., Ann Oncol, 2006

% (95% CI)SI 13 (10-15)NO, ma lo sapevano 50 (46-54)NO e non lo sapevano

27 (24-30)

NO, non so se sapevano

10 (8-14)

Quando la prognosi è diventata sfavorevole, è stato comunicato al paziente?

54 54

l’informazione sulla diagnosi di tumore secondo le risposte dei caregiver

M. Costantini et al., Ann Oncol, 2006

chi sono i pazienti chericevono più informazione

residenti nel nord Italia più giovani con titolo di studio elevato con tumori testa-collo o mammariocon aspettativa di vita lunga alla diagnosi

55

Il punto di vista dei pazienti

55

ITA UK IRL ISR KOR AUS USA PORT 0

25

50

75

100

% di pazienti oncologici che desiderano una onesta informazione sulla diagnosi nei diversi studi

Il punto di vista dell’opinione

pubblica

% di persone che desidererebbero una onesta informazione nel caso di una malattia mortale

ITA HK SPA TAI JAP 0

25

50

75

100

M. Costantini, 2008

56 56

M. Costantini, 2008

% di pazienti oncologici a cui è stata comunicata

la diagnosi di tumore nei diversi studi italiani

85-90 91-95 96-00 01-05 0

25

50

75

100

dal 1985 al 2005!

57 57

Comunicare in oncologia Quando? • Al momento della prima visita,

delineando tutte le varie possibilità terapeutiche in funzione dei possibili risultati?

• In maniera continuativa, durante le diverse fasi dela evoluzione clinica della malattia?

58 58

Comunicare in oncologia A chi? • Ogni tipo di comunicazione deve

essere attuata tenendo ben presente la persona malata, nella sua complessità ed interezza, valutando le sue specifiche caratteristiche umane, i suoi problemi e le sue preoccupazioni familiari, le sue incertezze e le sue paure sociali, insieme alle caratteristiche cliniche della neoplasia.

59 59

Caso clinico

• Paziente di 41 anni, importante dirigente di industria.

• Viene operata per una carcinoma della mammella ad alto rischio e deveessere sottoposta a chemioterapia e ad ormonoterapia per 5 anni.

• … ma aveva deciso di avere dei figli con il suo nuovo compagno!

60 60

A chi?

• La familiarità e la predisposizione genetica.

61 61

Caso clinico

• Donna di 36 anni, 3 figlie, M5 e O3, viene operata per un carcinoma ovarico.– Paura per le figlie.– Interessi conflittuali con i familiari.

62 62

Comunicare in oncologia Come? • Numeri, percentuali, numeri…• Facile, poco coinvolgente,

apparentemente molto tecnico.• Ma le percentuali si riferiscono a

popolazioni e non al singolo paziente che sied di fronte a noi!

63 63

La comunicazione in oncologia.

Necessità clinica o inutile complicazione assistenziale?

64

Study of unmet needs in symptomatic veterans with advanced cancer

• The total number of unmet needs was predictive of QOL.

64Shirley S. Hwang et al., 2004

65

End of life issues and spiritual histories

• Patients facing end-of-life issues have spiritual concerns that may have an impact on their medical decision-making.

• Conclusion:– Spiritual concerns of many patients facing

end-of-life decisions are not being addressed.

King DE e al (2003) End of life issues and spiritual histories South medical Journal 96: 391- 393.

66

Religious struggle as a predictor of mortality among medically ill elderly patients.

• Although church attendance has been associated with a reduced risk of mortality, no study has examined the impact of religious struggle with an illness on mortality.

• Certain forms of religiousness may increase the risk of death.

• Elderly ill men and women who experience a religious struggle with their illness appear to be at increased risk of death, even after controlling for baseline health, mental health status, and demographic factors.

66Pargament Kl e al (2001) Religious struggle as a predictor of mortality among medically ill elderly patients. Archives Internal Medicine. 161: 1881-85.

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Breast cancer in the family

• Children's perceptions of their mother's cancer and its initial treatment .

68

Breast cancer in the family

• Family fatigue

69

Cancer survivors with unmet needs were more likely to use complementary and alternative

medicine.

– Despite advancements in cancer care, cancer survivors continue to experience a substantial level of physical and emotional unmet needs.

– Cancer survivors who experienced unmet needs within the existing cancer treatment and support system were more likely to use CAM to help with cancer problems.

JJ Mao et al., J Cancer Surviv. 2008

70

Simultaneous care

Terapia di supporto

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