Cancer Survivorship: Meeting the Needs of a Growing Population

Transcription

1 Cancer Survivorship: Meeting the Needs of a Growing Population Ann H. Partridge, MD, MPH 2018 Master Class Course

2 Disclosure I have nothing to disclose. Off Label/Investigational Discussion In accordance with Annenberg Center policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.

3 Which one of the following is least prevalent in cancer survivor populations? A. Depression B. Fatigue C. Cognitive dysfunction D. Sexual dysfunction E. They all occur around the same prevalence

4 Which one of the following cancer survivor populations are generally not recommended to undergo routine surveillance imaging for recurrence in follow-up? A. Men and women with early stage colon cancer B. Women with early stage breast cancer who undergo BCT C. Men and women with history of lung cancer D. Men on ADT for early prostate cancer E. None of the above (all should undergo imaging in f/u)

5 Number of US Cancer Survivors: in Millions 20 Million Million Based on data from Surveillance Epidemiology and End Results.

6 Current and Projected Cancer Survivors in US: Proportion by Site of Disease Miller et al., CA Cancer J Clin million survivors 18 million survivors 15 million survivors 20 million survivors 6

7 What is Survivorship? The National Cancer Institute s (NCI) Office of Cancer Survivorship and the National Coalition for Cancer Survivorship s (NCCS) definition of survivorship: from the time of diagnosis and for the balance of life Includes not only the individual with cancer, but also family and loved ones In practice: survivorship usually focuses on the period in the cancer continuum after the completion of early active treatment

8 Survivorship Spans the Cancer Journey Pre-Diagnosis Diagnosis & Treatment Palliative Care; End of Life Needs vary between individuals Needs vary within individuals along the continuum Adapted from NCI, 2005

9 What are the medical and psychological needs of cancer survivors? Non-Cancer Related Medical Care Health promotion/disease prevention Chronic care (e.g. diabetes) Unrelated cancer screening Cancer Related Medical Care Surveillance/prevention of recurrence or new primary breast cancer Screening and treatment of complications of treatment Related cancer screening Counseling/support re: cancer related lifestyle recommendations and cancer-related health decisions Psychosocial Care Attention to quality of life, fear of recurrence, depression, anxiety Financial burden Family/genetic counseling Coordination of Care Between Primary Care, Oncology, and Other Providers 10 Nekhlyudov and Partridge, 2013

10 Increasing Focus of Research on Survivorship Figure 1. Survivorship study designs by year (Harrop et al. Cancer Epidemiol Biomarkers Prev. 2011;20: )

11 A Growing Number of Guidelines- New ASCO/ACS Cancer Survivorship Care Guidelines 11

12 4 Major Areas of Focus in Cancer Survivorship Recurrence and new cancers Long-term and late effects Modifiable health behaviors Coordination of care provider-provider patient-provider

13 Surveillance, screening and prevention of recurrence and new cancers

14 To scan or not to scan Rationale for screening for recurrent cancer: Detection of asymptomatic disease would improve morbidity or mortality Lead to earlier additional testing and potential early intervention Is cost-effective and safe in a population Makes sense for that individual patient 14

15 Evidence for CEA and CT Follow-up in Colorectal Cancer Survivors 1202 stage 1-3 dz randomized (2x2) to CT q 6-12 mos and/or CEA q3-6 mos Primrose JN, et. al. JAMA 2014;311:

16 Evidence for CEA and CT Follow-up in Colorectal Cancer Survivors Intensive follow-up by either CEA or CT increased the likelihood of detecting a recurrence that can be treated with curative intent No advantage seen to combining both strategies Absolute difference in the proportion of participants treated with curative intent was approximately 5% in the ITT analysis (8% in the evaluable subset) Primrose JN, et. al. JAMA 2014

17 ASCO Guideline Recommendations Medical history, physical examination, and CEA assay every 3-6 months for 5 years 80% of recurrences occur during the first years and 95% by 5 years CT imaging annually for 3 years no justification for surveillance PET/CT scan testing Meyerhardt et. al. J Clin Oncol 2013

18 Evidence for how breast cancer patients should be followed for recurrence 18 GIVIO Investigators. JAMA.1994;271(20):

19 Important lessons learned in screening for breast cancer recurrences Most (~75%) symptoms not related to recurrence Most (~75%) recurrences heralded by symptoms Only a minority (< 25%) of recurrences are detected in asymptomatic patients Lab and radiology tests have significant false-positive rates excess evaluation and anxiety Patients can be educated about this 19

20 Follow-up for NSCLC Survivors: Heterogeneity in Recommendations Chen Y. et al, Lung Cancer 2016

21 Summary of Screening for Recurrence - H & P - Chest scans q3-6 mos x 2yrs, then annually - H & P - Mammography if BCT/contralateral breast remains - No imaging or bloodwork otherwise - H & P - scans and bloodwork, tailored - H & P - PSA q 6 mos x 5, then q yr - DRE annually - H & P - Scans and bloodwork, tailored - H & P, pelvic - Scans and bloodwork - tailored - H & P - CEA q3-6 mos x 5 yrs - CT q12 mos x 3 yrs

22 New primary disease risk: update family history and re-visit genetics Survivorship care should entail updating family history and revisiting genetic issues (re-) testing as needed Furthermore Barriers to testing at diagnosis may have diminished Testing is evolving Patient and systems level indications for testing are evolving Ruddy et. al. J Clin Oncol 2016

23 Prevention and Management of Long-term/Late Effects

24 Local Therapy (Surgery and Radiation) Effects: Think Field/Site Specific Problems Pain, numbness, lymphedema, restricted motion or weakness Cellulitis, nerve damage, bone fracture, pneumonitis, lung fibrosis Functional, cosmetic or reconstruction changes Heart disease, sarcomas, skin and other second cancers, lung fibrosis Systemic effects from site-specific treatment (e.g., hypothyroidism, hypogonadism)

25 Systemic Therapy (Chemotherapy, Hormonal Therapy and Biologics): A Systems Approach

26 Effects of Androgen Deprivation Therapy

27 Effects of Androgen Deprivation Therapy

28 Metabolic and Cardiovascular Effects of ADT ADT is associated with unfavorable metabolic changes No randomized trials have prospectively addressed cardiovascular risk of ADT Retrospective data are available from randomized trials and large observational series Among 4141 men from 8 randomized trials, CV death in men receiving ADT versus control was not different Men with 2 CV events, with the latest within 1 year of ADT, were at the highest risk of a CV event within the first 6 months of ADT Nguyen et al, JAMA, 2011; O Farrell et al, JCO, 2015

29 Sexual Dysfunction: Reported in ~25-50% of Survivors Treatment depends on primary problem (often multifactorial) ERT/Topical E2 if appropriate, or non-hormonal water-based vaginal lubricants for dyspareunia Vaginal dilation for stenosis Consider medications for libido problems Sex therapy; couples counseling, psychotherapy Comprehensive assessment and targeted intervention WORKS! RCT of 76 breast cancer survivors Usual care vs treatment with assessment, education, counseling, and interventions directed at severe menopausal symptoms Treatment group reported improved menopausal symptoms (P =.0004) and sexual functioning (P =.04) 29 Schover L et al., European Journal of Cancer, 2014; Ganz PA, et al. JNCI. 2000

30 For Men: Management of ED Modify reversible causes First-line therapy Second-line therapy Third-line therapy Medication change or discontinuation Lifestyle modification Hormone replacement Oral erectogenic agent Vacuum erection device Couples /sexual therapy Intracavernosal self-injection Intraurethral alprostadil Surgical prosthesis Vascular reconstruction Process of Care Consensus Panel. Int J Impot Res. 1999

31 Randomized Blinded Sham- and Waitlist-Controlled Trial of Acupuncture for Joint Symptoms Related to Aromatase Inhibitors in Women with Early Stage Breast Cancer (SWOG 1200) True Acupuncture True Acupuncture No Acupuncture 2 2x week x 6 weeks 1x week x 6 weeks 12 weeks AI > 3/10 Worst Pain N=226 1 Sham Acupuncture 2x week x 6 weeks Sham Acupuncture 1x week x 6 weeks No Acupuncture 12 weeks 1 Wait List Control Wait List Control Wait List Control 6 weeks 6 weeks 12 weeks Assessment Week Presented with permission, Hershman et al., SABCS 2017

32 Significant Improvement in Pain from True Acupuncture Linear Mixed Model - Worst Pain (BPI) Sustained over tapered treatment, and for 12 weeks beyond Improvements also seen with true acupuncture on multiple additional measures of pain/stiffness Toxicity minimal Presented with permission, Hershman et al., SABCS 2017

33 Acupuncture for all with AIMSS? Large, well-designed multi-center NCI-sponsored study Other options: pharmacologic, physical therapy, other integrative therapies have limited efficacy Acupuncture may also help with fatigue, peripheral neuropathy, hot flashes, chronic pain syndromes, nausea, anxiety, stress Unanswered questions: Long-term durability? Need for maintenance? boosters? Generalizable to wider population? Acupuncture highly operator-dependent, not easily manualized Cost and access issues Insurance coverage limited, narrow indications Roberts et al., Crit Rev Oncol/Hemat 2015

34 Screening and Prevention of Late Effects Many unanswered questions- cardiac and bone health recommendations Secondary malignancies- e.g., lung after lung cancer, bowel and bladder after prostate HD or Lymphoma s/p chest irradiation- 148 women with HD s/p chest RT age < 35, at least 8 years prior Followed for 3 years with annual mammogram and MRI 63 biopsies in 45 patients (30%) 18 of 63 biopsies (29%) showed malignancy Sensitivity 63% for MRI; 68% for mammogram Sensitivity for both MRI and mammogram together: 95% All but 1 of the image detected malignancies were pre-invasive or sub cm and all were node negative (Ng et al, JCO 2013) ACE inhibitor etc. for prevention of cardiac complications after xrt, anthracyline therapy Low dose tamoxifen for prevention of breast cancer Many studies ongoing and reporting out- e.g.:

35 Fertility Preservation in People Treated for Cancer Assessment of risk for infertility Communication with patient Patient at risk for treatment induced infertility - Patient interested in fertility preservation options Refer to specialist with expertise in fertility preservation Eligible for proven fertility preservation method Male: Female: sperm cryopreservation Embryo cryopreservation Oocyte cryopreservation 2012 oophoropexy conservative gynecologic surgery 2015? Investigational fertility preservation technique* Cryopreservation of testicular or ovarian tissue *Clinical trial participation encouraged Ovarian suppression Modified from Lee et al., J Clin Onc; 2006

36 Study Methods Systematic review and meta-analysis of individual patient data from RCTs that investigated the role of temporary ovarian suppression with GnRHa during chemotherapy for early breast cancer patients 13 RCTs n=1,581 Included Not included 5 RCTs (3 positive and 2 negative) n=873 (55.2%) 8 RCTs (5 positive and 3 negative) n=708 (44.8%) PROSPERO registration number: CRD Lambertini et al, JCO, in press

37 Study Characteristics Definition of POI PROMISE-GIM6 1,2 No resumption of menstrual activity and postmenopausal levels of FSH and E2 POEMS/SWOG Moffitt-led trial 4 GBG-37 ZORO 5 Anglo Celtic Group S OPTION 6 Amenorrhea for the prior 6 months and postmenopausal levels of FSH No maintenance of menses and no resumption of menses No re-appearance of two consecutive menstrual periods within 21 to 35 days Amenorrhea with elevated FSH Timing of POI after chemotherapy 12 months 24 months 24 months 6 months Between 12 and 24 months Sample size ER status for eligibility ER-positive and ERnegative ER-negative only ER-positive and ERnegative ER-negative only ER-positive and ERnegative Upper age limit for eligibility 45 years 49 years 44 years 45 years None Type of GnRHa Triptorelin Goserelin Triptorelin Goserelin Goserelin 1. Del Mastro L et al, JAMA 2011;306: Lambertini M et al, JAMA 2015;314: Moore HCF et al, N Engl J Med 2015;372: Munster P et al, J Clin Oncol 2012;30: Gerber B et al, J Clin Oncol 2011;29: Leonard RCF et al, Ann Oncol 2017;28: Lambertini et al, JCO, in press

38 Premature-Ovarian Insufficiency Rate 50% 40% Similar improvement in amenorrhea rates at 2 years OR* 0.38 (95% CI ) Meta-analysis approach p< % 30.9% 30% 20% 10% 0% GnRHa group n=363 Control group n=359 *Odds ratio (OR) adjusted for age, estrogen receptor status, type and duration of chemotherapy administered Lambertini et al, JCO, in press

39 Post-Treatment Pregnancy Rate GnRHa Group: 37/359 (10.3%) vs. Control Group: 20/367 (5.5%) Meta-analysis approach IRR* 1.83 (95% CI ) p=0.030 Age distribution, years Estrogen receptor status Positive Negative GnRHa group (n = 37) No. (%) 37 (100) 0 (0.0) 6 (16.2) 31 (83.8) Control group (n = 20) No. (%) 20 (100) 0 (0.0) 2 (10.0) 18 (90.0) *Incidence rate ratio (IRR) Lambertini et al, JCO, in press

40 Disease-Free Survival Estrogen receptor-positive disease Estrogen receptor-negative disease HR* 1.17 (95% CI ) HR* 0.95 (95% CI ) *Hazard ratio (HR) adjusted for age, estrogen receptor status, type and duration of chemotherapy administered and tumor stage p interaction =0.867 Lambertini et al, JCO, in press

41 Overall Survival Median follow-up = 5.0 years (IQR, years) HR* 0.67 (95% CI ) p=0.083 *Hazard ratio (HR) adjusted for age, estrogen receptor status, type and duration of chemotherapy administered and tumor stage Lambertini et al, JCO, in press

42 Azim et al JCO 2012 Is it safe to become pregnant after breast cancer?: Matched analysis

43 Pregnancy after Breast Cancer Is it Safe? The Bottom Line: No clear adverse effect of subsequent pregnancy on prognosis from retrospective data (caveat: healthy mother bias) Conventional wisdom is to wait until >2 years, to get through early risk of recurrence period or receive endocrine therapy No data to suggest harm in pregnancy sooner Ultimately the decision to get pregnant is a very personal one

44 Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsive Breast Cancer IBCSG / BIG 8-13 ALLIANCE # A POSITIVE TRIAL INTERNATIONAL PI: OLIVIA PAGANI NORTH AMERICAN PI: ANN PARTRIDGE

45 The POSITIVE Trial: Endocrine therapy interruption for pregnancy in breast cancer patients Phase II trial designed to evaluate safety and pregnancy outcomes of interrupting ET for young women with ER+ disease who desire pregnancy Enroll 512 women, <42, premenopausal, have completed between months of ET Study participants come off endocrine therapy for up to 2 years for a pregnancy attempt, restart hormonal therapy Outcomes: disease, reproductive, psychosocial

46 Survivors Often Experience A Roller Coaster of Emotions Isolation, Fear, Anger, Grief, Anxiety, Depression

47 Mental Health in Cancer Survivors Depression and anxiety in survivors Associated with symptom distress, maladaptive coping Depression associated with heightened risk for premature mortality (RR ) and cancer death (RR 1.18) Increased rates of suicide among populations of long-term breast and testicular cancer survivors Screen in your clinic Reassure, treat or refer as appropriate Guidelines from NCCN at and from ASCO at Andersen et al, JCO 2014

48 Common Symptoms Overlap in Survivors Depression Fatigue Cognitive Dysfunction

49 Prevalence of Symptoms in Survivors 40% % of Patients 35% 37% 30% 32% 25% 20% 15% 10% 14% 5% 0% Depression Fatigue Cognitive dysfunction Krebber et al. (2014) PsychoOncology Cella et al. (2001) Journal of Clinical Oncology Minisini et al. (2004) Lancet Oncology

50 Treatment Considerations Depression Cognitive-Behavioral Therapy Fatigue Exercise Cognitive Dysfunction Neuropsychological (e.g., memory/attention behavioral training) Pharmacotherapy Third-Wave Psychotherapies (ACT, mindfulness meditation etc.) Distraction (e.g., socialization) Complementary Therapies (sleep, yoga, psychosocial stress reduction etc.) Stimulants??? Adaptive Computerized Training? Exercise? Medicinal (gingko biloba, methylphenidate)??? Guidelines from NCCN at and from ASCO at

51 Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis Meneses-Echavez et al, BMC Cancer, 2015

52 Improving Health Behaviors: Can we capitalize on the teachable moment?

53 Energy balance matters for cancer survivors Risk of weight gain, obesity and metabolic syndrome in breast, colorectal, prostate, testicular, pediatric cancer survivors Effects cancer outcomes in breast, colorectal and prostate survivors Effects cardiovascular and overall mortality Fortunately Physical activity, diet and attention to diabetic and cardiovascular risk factors likely helps Associated with lower risk of cancer recurrence and death Ligibel and Meyerhardt, UpToDate, last accessed

54 Physical Activity and Breast Cancer Survivorship: Results from the Nurses Health Study Recurrence * BRCA Death # Total Death # MET-Hrs/week 3> *p=0.05, # p<0.004 Holmes MD, et al. JAMA. 2005;293(20):

55 Hazard Ratio for Cancer Recurrence or Death Dietary Patterns and Stage III Colon Cancer Western diet Prudent diet Quintiles of Dietary Pattern P, trend < Other data suggest high glycemic load particularly risky Meyerhardt, J. et al. JAMA (7):

56 WINS Study: Impact of Low-fat Diet on RFS in Breast Cancer Survivors Chlebowski RT, et al. J Natl Cancer Inst. 2006;98(24):

57 Womens Healthy Eating & Living Study (WHEL) RCT to fruit, vegetable, and fiber among breast cancer survivors intervention control Monthly telephone counseling and group sessions Observational studies: Soy, Alcohol, Marine fatty acids Banked bloods from years 1,2,3,4,5 Pierce JAMA 2007

58 American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Survivors Achieve and maintain a healthy weight If overweight or obese, limit consumption of high-calorie foods and beverages and increase physical activity to promote weight loss Engage in regular physical activity Avoid inactivity and return to normal daily activities as soon as possible following diagnosis Aim to exercise at least 150 minutes per week. Include strength training exercises at least 2 days per week. Achieve a dietary pattern that is high in vegetables, fruits, and whole grains Follow the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention Rock et al., CA Journal for Clin 2012

59 Future Directions Prospective exercise and weight loss studies ongoing Prospective RCTs ongoing testing NSAIDS

60 Modifiable Health Behaviors for Cancer Survivors Habits to DROP or DECREASE Habits to MAINTAIN OR INCREASE Tobacco Alcohol High risk sexual behavior Illicit drug use Physical activity Prudent diet Weight management COMMON SENSE!

61 Coordination of Care: How can we deliver all of this care effectively and efficiently?

62 Follow-Up Care Standards for Breast Cancer What Do You Need to Consider for Every Patient? When and with whom over time? ISSUE Standard of Practice / Recommendation Visit Frequency Diagnosis History, exam +/- lab with? Screening & Routine lab work NO Imaging- Screening for Recurrence NO Disease and risk-based Bone density YES Site Specific Screening Echocardiogram If issue Mammogram If remaining breast tissue Breast MRI If high risk Counseling Genetics Fertility and contraception Psychosocial Disease & Site Specific Counseling Follow-up Health behaviors Sexual functioning Calcium/Vitamin D Lymphedema, chemobrain, hot flashes, menopausal symptoms Primary Care Vaccine schedule GYN follow up

63 Treatment Summaries & Survivorship Care Plans Can help to communicate your tailored needs New tools, apps ASCO ACS

64 ACS Cancer Survivorship Care Guidelines: Clinician Mobile App 64

65 In Conclusion Enormous progress has been made yet many challenges (opportunities!) remain in optimizing cancer survivorship care Awareness of what does help our patients and good communication with them and their other providers are both critical factors Increased focus on the importance of the survivorship phase of care in care and research, along with improvements in technology and self-management should lead to better outcomes