Brachyterapia Pulsacyjna

Follow-up, supportive care

Janusz Skowronek, MD, PhD, Associate Professor | Department of Brachytherapy | Greater Poland Cancer Centre, Poznan, Poland www.wco.pl/zb

Educational Workshop Masterclass: Brachytherapy in Partial Breast Irradiation Euro-Asian Breast Brachytherapy School, Erlangen, Germany, 9-10 October 2014 Factors influencing cosmetic effect

1. location of the tumor (EUQ vs other),

2. tumor size (T1 vs. T2),

3. radiotherapy technique,

4. irradiation of regional lymph nodes,

5. dose fractionation,

6. dose rate,

7. systemic adjuvant therapy. American Brachytherapy Society - Breast Brachytherapy Task Group Martin Keisch, M.D., Douglas Arthur, M.D., Rakesh Patel, M.D., Mark Rivard, PhD., Frank Vicini, M.D. ; February, 2007 Post-Treatment Evaluation 1. Mammographic assessment: 1.1. Serial Mammography baseline at 4-6 months and then as per institutional protocol

2. Physical examination: 2.1. Cosmetic evaluation 2.2. Examination for recurrence 2.3. Examination for complications

3. Quality of Life: 3.1. Patient satisfaction should be assessed

4. Post-Treatment Biopsy: 4.1. As needed to rule out recurrence versus fat necrosis

Partial breast brachytherapy after lumpectomy: low-doserate and high-dose-rate experience Arthur DW, et al. Int. J. Radiation Oncology Biol. Phys., Vol. 56, No. 3, pp. 681–689, 2003 Early and locally advanced breast cancer: diagnosis and treatment Full Guideline; February 2009 Developed for NICE by the National Collaborating Centre for Cancer Follow-up Includes: 1. clinical and radiological options for assessment of both the treated and the contralateral breast. 2. It incorporates supervision of ongoing adjuvant treatment and potential side effects, and review of patients who are in clinical trials. 3. Follow-up should also include advice on general health, diet and exercise.

1. Goldhirsch A, Winer EP, Coates AS i wsp. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206–2223. 2. Khatcheressian JL, Hurley P, Bantug E i wsp. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31: 961–965. 3. Senkus E, Kyriakides S, Penault-Llorca F i wsp. ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (supl. 6): vi7–vi23. Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up The main objectives checkups after treatment for breast cancer are:

1. early detection of local and regional recurrence and secondary cancers, 2. observation towards late complications (also related to the earlier menopause and osteoporosis), 3. advisory psychological and sociological (including recommending physical activity and a proper diet to reduce overweight (BMI)), 4. the assessment of the late results of treatment. Is less relevant however the active search of asymptomatic distant metastases because their earlier detection as a result of the expanded range of checkups has no significant impact on the effectiveness of treatment and quality of life.

Khatcheressian JL, Hurley P, Bantug E i wsp. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31: 961–965. Senkus E, Kyriakides S, Penault-Llorca F i wsp. ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (supl. 6): vi7–vi23. Rojas MP, Telaro E, Russo A i wsp. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev 2005 Jan 25: CD001768. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators JAMA 1994; 271: 1587–1592. Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up The rules for follow-up of patients after radical treatment of noninvasive ductal carcinoma and cancer in invasive stage I-III Examination Frequency Self-examination Monthly First 2 years – every 3 months1 Clinical examination 2–5 years every 6 months > 5 years every 12 months

Mammography2 Every 12 months; first - after 6 months

GYN examination Every 12 months in woman treated with tamoxifen3 Diagnostic imaging and laboratory Only by clinical indications Evaluation of bone mineralization Every 12–24 months (densitometry)4 BMI Recommended BMI: 20–25

1In preinvasive cancer checkups every 6 months for the first 2 years, then every 12 months; 2MR to consider in patients carriers of mutations in the BRCA genes; 3In patients without symptoms related to genital tract there is no indication to perform intravaginal ultrasound and endometrial biopsy; 4concerns patients at high risk for osteoporosis due to therapy with an aromatase inhibitor or the inhibition of ovarian hormonal activity; BCT (breast conserving treatment) Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up

1. The most important in the diagnosis of recurrent disease is physical examination and history. 2. Physical examination should include the opposite breast (in the case of bilateral breast- conserving therapy), chest wall and bilateral axillary nodes and cervical-supraclavicular. 3. You should evaluate the condition of the skeletal system and pay attention to the possibly presence of edema of the arm on the side of the affected breast, also examine the abdominal cavity, heart and lungs. 4. The history should take into account the general symptoms (lack of appetite, weight loss, fatigue, insomnia), bone pain, symptoms of respiratory (cough, shortness of breath), neurological symptoms (headache, nausea, vomiting, confusion, weakness, numbness, tingling ), symptoms of gastrointestinal symptoms (abdominal pain, constipation, bleeding), and symptoms of urogenital (vaginal bleeding, pelvic pain, difficulty in passing urine). 5. Should be evaluated patient's mental state and the presence of symptoms of endocrine (hot flushes, dyspareunia, vaginal dryness, sexual disorders).

1. The only recommended imaging study within control after treatment is X-ray mammography (MMG). 2. It has been demonstrated that regardless of the age of the patients, MMG performed every 12 months allows for reduction in the mortality risk from breast cancer. 3. In patients treated with BCS first control MMG should be done after 6 months.

Schootman M, Jeffe DB, Lian M i wsp. Surveillance mammography and the risk of death among elderly breast cancer patients. Breast Cancer Res Treat 2008; 111: 489–496. Lash TL, Fox MP, Silliman RA. Reduced mortality rate associated with annual mammograms after breast cancer therapy. Breast J 2006; 12: 2–6. Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up

In patients without suspicious symptoms is not recommended testing laboratory tests (blood count, biochemistry), the concentration of serum tumor markers (CA15-3 / CA27.29, CEA) and other than the MMG imaging tests: abdominal ultrasound, chest X-ray, CT, MRI, PET and bone scintigraphy, because there was no effect of these methods on survival time.

In patients with an intact uterus who receive supplementary treatment with tamoxifen, there is an increased risk of endometrial cancer and in this group every 12 months should be performed gynecological exam. Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up 1. In patients with a family breast cancer history should be reconsidered genetic testing towards the mutation carriers BRCA, if it was not performed before. 2. Features of clinical-pedigree associated with increased probability of BRCA carriers include: a. breast cancer before 40 years of age, b. multiple breast cancer and / or ovarian cancer in the family, c. history of other cancers, particularly ovarian cancer, d. bilateral breast cancer, e. breast cancer in men, f. "Triple negative breast cancer" patients before menopause, g. medullary or atypical medullary, h. Ashkenazi origin i. confirmed carriers of BRCA mutation in the family.

Zalecane badania kontrolne u chorych na raka piersi po radykalnym leczeniu (wg Jassem J, Krzakowski M. Rak piersi. W: Krzakowski M i wsp. (red). Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. Via Medica, Gdańsk 2013, str. 211-265) Follow-up 1. Patients should be encouraged to be physically active (at least 4 hours of exercise in week), avoidance of alcohol abuse and a proper diet in order to maintain body mass index in the range of 20-25. 2. Pregnancy after treatment for breast cancer does not increase the risk of recurrence. 3. A safe distance to be observed between completion of radical treatment and pregnancy has not been established . 4. Pregnancy is contraindicated in patients receiving complementary treatment with tamoxifen, and after its completion hormone therapy can be resumed.

There are no recommendations for regimen checkups in patients with metastatic breast cancer. Cosmetic Effect

N= Balloon (B) or Fibrosis Teleangiectasia CE – excellent/good Fat necrosis/ seroma Multicatheter (M) Polgár et al. 45 M Grade 3 – 2,2% Grade 3 – 0% 77,8% (2010) Benitez et al. 43 B 39,5% 81,3% Fat necrosis - 9,3% (2007) ASBS registry 1449 B 92,5 % at 4 yrs; Seroma – 23,9%, trial Vicini et al. 90.4% at 6 yrs Fat necrosis – 1.5% (2008) Dragun et al. 90 B 90% at 2 yrs (2007) Niehoff et al. 44 B 18% 75% (2006) Belakcimi et al. 43 B 84% at 1 yrs (2009) Dickler et al. 30 B 93% at 13 months (2005) Chen 199 M 46% 34% 99% at 5 yrs Fat necrosis -11% et al. (2006) Wazer et al. 75 M 91% at 6 yrs (2006)

The cosmetic outcomes and toxicity of MammoSite PBI are comparable to those seen after multicatheter-based. Cosmetic Effect Vicini et al. Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy Int J Radiation Oncol Biol Phys, Vol. 83, No. 2, pp. 512-518, 2012 Cosmetic Effect Vicini et al. Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy Int J Radiation Oncol Biol Phys, Vol. 83, No. 2, pp. 512-518, 2012 Cosmetic Effect Strauss et al. Accelerated partial breast irradiation utilizing balloon brachytherapy techniques; Radiotherapy and Oncology 91 (2009) 157–165 Seroma Evans et al. Persistent seroma after intraoperative placement of mammosite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors. Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 333–339, 2006  38 pts, MammoSite, follow-up - 17 months (median)  Seroma was verified by clinical examination, mammography, and/or ultrasonography.  Persistent seroma was defined as seroma that was clinically detectable >6 months after radiotherapy completion.  Seroma – 76,3 %; persistent seroma – 68,4% Conclusion:  Intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation is associated with a high rate of clinically detectable seroma that adversely affects the cosmetic outcome.  The seroma risk was positively associated with body weight and negatively associated with postprocedural infection. Seroma Evans et al. Persistent seroma after intraoperative placement of mammosite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors. Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 333–339, 2006

Gross pathologic specimen of excised persistent seroma cavity, exhibiting glistening fibrous capsule with thick, 2- mm fibrous rind (arrow). Sonogram of persistent seroma with irregular contour (arrow), prompting biopsy. Seroma Evans et al. Persistent seroma after intraoperative placement of mammosite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors. Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 333–339, 2006

Histopathologic features of excised persistent seroma cavity. Specimen exhibited squamous metaplasia (yellow arrow), active collagen deposition (blue arrow), and foreign body giant cell reaction (inset top left). Axial CT scan of patient with persistent seroma showing significant nodularity (arrow) on lateral aspect of cavity. Seroma Evans et al. Persistent seroma after intraoperative placement of mammosite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors. Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 333–339, 2006

Patient with persistent seroma 20 months after treatment. Residual seroma in upper outer quadrant (arrow) of right breast measures 5 cm on mammogram.

Mammogram, mediolateral oblique view, at 26 months after treatment with MammoSite in same patient pictured in right Fig. Seroma cavity has begun to mimic balloon shape. Seroma Evans et al. Persistent seroma after intraoperative placement of mammosite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors. Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 333–339, 2006 Conclusion: The high incidence of persistent seroma and the unusual fibroepithelial seroma capsule found in the current study after the intraoperative placement of the MammoSite catheter for APBI may be related to two central factors: 1. the physical effects of the inflated catheter on the postexcisional cavity, 2. and the influence of the inflated catheter and high dose radiotherapy on the cellular mechanisms associated with wound healing in the immediate postoperative period. Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

1. 171 women, APBI, HDR-BRT, 2. 34 Gy/10 fractions/1 week with two fractions/day after intraoperative/postoperative placement of catheters. Results: 1. Median follow up of 48 months – 20 women developed FN with median time to detection being 24 months (range: 4–62 months). 2. Actuarial 5 and 7 year FN rate was 18% and 23%, respectively. 3. Volume of excision was the only significant factor affecting FN (p = 0.04). Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

1. Fat necrosis can bes detected either by the presence of palpable mass, mammographically or in the presence of the above with pain. 2. Presence of oil cyst, coarse calcifications, increase density, architectural distortion and presence of spiculated mass are the criteria considered for the mammographic diagnosis of fat necrosis. 3. Whenever there is suspicion of recurrence fine needle aspiration cytology (FNAC) or biopsy of the breast tissue should be performed to rule out a local recurrence. Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

Actuarial incidence of fat necrosis in 171 women treated with interstitial brachytheraphy for accelerated partial breast irradiation. Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

Pseudocyst with calcification on Calcifications seen on mammogram mammogram in a patient with fat suggestive of fat necrosis necrosis Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

Incidence of fat necrosis in various series of APBI using high dose rate brachytherapy

Center (Author)ref No. of Brachytherapy Method of detection Incidence Time of Location of Additional Median follow Factors patients of fat necrosis of Fat detection of fat necrosis investigations up (months) affecting fat necrosis fat necrosis necrosis (months) National institute of 87 HDR 36.4Gy Clinical, 36.5% 17 Tumor bed- 47% 48 Bra cup size Oncology Lovey et al.. mammography, 84.2% pathology Tufts/Brown University, 33 HDR 34Gy Clinical, 24% 7.5 Tumor bed- 62% 33 Volume of Wazer et al. mammography,pathol 100% 150 and ogy 200%, no of dwell positions National Institute of 45 HDR 30.3Gy, MammogramClinical, 22% - - 2.2%(surgery) 81 - oncology, Polgar et al. 36.4Gy pathology London Regional 39 HDR 37.2Gy Clinical pathology 13% Within 60 - 91 - Cancer Center, Perera F et al. Virginia Commonwealth 31 HDR 34Gy Mammogramclinical 2% - - 0 42 - University, Arthur DW et al. University Hospital 33 HDR/PDR Mammogram 15% 25.6 - 0 35 - Earlangen, Ott OJ et al. William Beaumont 79 HDR 32Gy, Mammogram clinical 11 66 - 7.3% 60 - Hospital, Vicini et al, 34Gy (surgery) Chen Y et al. Present study 171 HDR 34Gy Clinical, 18% 24 Tumor bed 45%(biopsy,e 48 Volume of mammography, 100% xcision excision pathology biopsy) Fat necrosis Budrukkar et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy; Radiotherapy and Oncology 103 (2012) 161–165

Suggested modifications in the classification of fat necrosis by Lovey et al.

Grade Presentation

Grade 0 No fat necrosis

Grade I Asymptomatic, only radiological cytological or biopsy (core, incision, excision) confirmation

Grade II Symptomatic fat necrosis not requiring medication; Palpable mass with or without pain

Grade III Symptomatic fat necrosis requiring medications

Grade IV Painful fat necrosis requiring surgery for symptom relief Fat necrosis Lovey et al. Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole- breast radiotherapy — 4-year results of a randomized trial; Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 724–731, 2007 c b a d

Radiologic features of fat necrosis. (a) Oil cysts without calcification; (b) pseudocyst with benign-type macrocalcification; (c) pseudocysts with ring-like coarse calcification; (d) benign-type macrocalcification without cyst formation. Cavity Visibility Score = CVS

British Columbia Cancer Agency Seroma Clarity Scale

0 = no visible seroma 1 = scar/shadow 2 = seroma identifiable with significant uncertainties 3 = seroma identifiable with minor uncertainties 4 = seroma easily identifiable, generally homogeneous with slightly blurred margin 5 = seroma easily identifiable, homogeneous with sharp boundaries

Thank you

35 Brachyterapia raka piersi 27.05.2011