PALIAŢIA, Vol 8, No 3, July 2015PALIAŢIA, Vol 8, No 3, July 2015 6 QoL is defined as the...

PALIAŢIA, Vol 8, No 3, July 2015

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PALIAŢIA, Vol 8, No 3, July 2015 ISSN 1844 – 7058 CONTENT EDITORIAL Sustainable palliative care? Heuvel van den WJA ORIGINAL PAPERS Bringing bad news at patients with lung cancer Tuinea AL, Rahnea Niță G, Dascălu D, Ioniță A, Crăciun M, Ciuhu AN Metastatic breast cancer management: a 5 cases Quality of Life analysis Niţipir C, Butolo AC, Iaciu C, Opriță A, Popescu B, Radu I, Costin R, Barbu MA CLINICAL LESSONS Metastases to the breast - differential diagnosis from primary breast carcinoma: case report Niţipir C, Popescu B, Butolo AC, Iaciu C, Opriță A, Costin R, Radu I, Barbu MA Palliative chemotherapy and best supportive care for stage IV ovarian cancer patient Radu I, Barbu MA, Popescu B, Velescu S, Dr Nițipir C NEW PUBLICATIONS

Pregnancy and cancers: from diagnosis to treatments Investigating Barriers to Access and Delivery of Palliative Care for Persons with Dementia in London, Ontario Quality Indicators to Improve Palliative Care in Flanders, Belgium

NEWS The picture on the cover: Storm coming (acryl) from Wim van den Heuvel, The Netherlands, (2011)


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EDITORIAL

Sustainable palliative care? Prof Dr Wim JA van den Heuvel, Chairman of Editorial Board of PALIAŢIA During the last ten years many initiatives were developed to stimulate palliative care in Europa. The number of resolutions, white papers, and recommendations is overwhelming, which shows the interest in palliative care by many citizens and organisations. Indeed, palliative care gets a lot of support, at least in words and on paper. However, a question which needs to be investigated is: what happens in practice with all these good intentions. The Council of Europe (by the way the oldest political European organisation) adopted unanimously a resolution in 2008, drafted by Dr. Wodarg from Germany, which recommended that palliative care should be included in the health policies of its member states. ‘Reducing the intensity of patients’ suffering should not be considered a luxury‘, stated the Council of Europe. However, anno 2015, it still is a luxury in many European countries. The last decade, enthusiastic national en international NGO’s started new actions together with professionals and involved citizens to promote palliative care. In 2005 the monthly e-mail Newsletter ‘The Palliative Care in Central and Eastern Europe (CEE) Countries’ was started by the Hungarian Hospice-Palliative Association. The Newsletter was – despite its useful information for CEE countries and international support - last published in 2012. The Croatian Association of Hospice friends, founded with support of the Croatian Ministry of Health ten years ago, posted its latest news in April 2012. The strategic plan 2014-2015 of the Croatian Ministry of Health does not include palliative care. In 2006 a project was started to develop ‘Regional Expertise Centres for Palliative Care in Romania’ (REPACARO).The outcomes of the project were presented on an international workshop in 2009, but despite various plans to do so not implemented yet in Romania. What still is available on line is PALIATIA. Recently the European Association of Palliative Care (EAPC) published a White Paper on outcome measurement in palliative care: Improving practice, attaining outcomes and delivering quality service. The White Paper contains 12 recommendations on outcome measurement, including patient-reported outcomes, in palliative care in clinical practice and research. Also attention is given to barriers and facilitators to implementing outcome measurement in clinical care. (see http://www.eapcnet.eu/Portals/0/Clinical/Publications/PM2015_Bausewein.pdf ). Indeed outcome measurement plays an increasing role in improving the quality, effectiveness, efficiency and availability of palliative care. Several doctoral theses were published recently (see NEW PUBLICATIONS in this issue). Besides, a standard set of outcome measures are helpful to understand different models of palliative care across countries. And models of palliative care do vary, if they are available at all. Besides the question raised in the beginning of this editorial ‘what happens in practice with all these good intentions’ and despite the valuable recommendations of the recent EAPC White Paper, an important question needs priority to be answered: how to reach sustainable palliative care for all people? We could start to learn in Europe.

http://www.eapcnet.eu/Portals/0/Clinical/Publications/PM2015_Bausewein.pdf


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ORIGINAL PAPERS

Bringing bad news at patients with lung cancer Dr Antuanela Loredana Tuinea (a,b), Dr Gabriela Rahnea Niță (a,c), Doința Dascălu (a,d), Aurora Ioniță (a,d), Mihaela Crăciun (a,d), Dr Anda Natalia Ciuhu (a,e) (a): Department of oncology – palliative care, Chronic Disease Hospital "St. Luke "Bucharest, Romania (b): MD, oncologist, palliative care specialist (c): MD, PhD, oncologist, palliative care specialist, trainer in palliative care (d): nurse (e): MD, PhD Student, oncologist, palliative care specialist Corresponding author: Dr Gabriela Rahnea Nita, e-mail: [email protected] Abstract Background: Communication may improve the quality of patients’ adaptation to the disease, reduce pain and physical symptoms, increase adherence to treatment and therefore lead to a higher degree of satisfaction with care Materials and method: We investigated 62 patients with lung cancer, who were hospitalized in the Hospital ‘’St. Luke’’, at the Oncology Palliative Care Department. Patients were asked to complete a questionnaire with nine questions (with yes/no answer) on how the patient wanted to be informed about some aspects of the disease. Results and discussions: Regarding the desire to be informed about the diagnosis of illness, disease status and prognosis changes over 80% of patients answered that they wanted to be informed. Four out of ten patients consider that the family and patient must be informed at the same time about diagnosis and prognosis; half of the patients did not answer this question. Some patients indicated that they wanted the presence of his/her spouse or another family member during the process of bad news communication. Conclusions: The ideas, concepts about the disease, the psychological and supportive resources, when illness occurs, family situation, reaction to difficult situations, personality, are factors that may explain differences in reaction to the impact of the disease. These factors may also relate to the way patients want to be informed about their disease. The opinion of the way the patient wants to be informed is important and should be respected. For health care professionals such knowledge is also important. Key words: bad news, communication, lung cancer, patient, family (Full text in Romania)


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Metastatic breast cancer management: a 5 cases Quality of Life analysis Cornelia Nitipir (a,b), Andra Cătălina Butolo (b), Cristian Iaciu (b), Alexandru Opriță (b), Bogdan Popescu (b), Irina Radu (b), Răzvan Costin (b), Maria Alexandra Barbu (b)

(a): MD, PhD, senior oncologist, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania (b): MD, oncologist, Elias Emergency University Hospital, Department of Oncology, Bucharest, Romania Corresponding author: Dr Niţipir Cornelia, e-mail: [email protected] Abstract Background Breast cancer is the most common female cancer worldwide with an incidence increasing by 1% yearly. About 20% of breast cancer patients present metastases and around 50% of those with an operable breast cancer experience relapse. Despite the new era of cancer treatment, the average survival for patients with metastatic breast cancer is still between 2 and 4 years. The quality of life of these patients should be one of the primary end points of the treatment. Case series We present an analysis of a 5 cases of patients with metastatic breast cancer showing that chemotherapy, immunotherapy and osteoclast inhibitors modified the levels of quality of life by significantly improving it. The patients filled in a questionnaire (Edmonton Symptom Assessment System) to assess their quality of life before treatment initiation in our clinic, after the first 3 cycles of chemotherapy, and after the last cycle. We found that quality of life was improved especially in terms of pain control, relief of tiredness, appetite and well-being. Despite disease progression and development of new metastasis, the patients did not experience important changes in their clinical status. They maintained a good performance status that allowed us to alternate multiple lines of therapy and to control the disease with minimal toxicity. Conclusion Metastatic breast cancer is a disease with a long natural evolution, but a well conducted treatment with a multidisciplinary approach may achieve a quality of life comparable with that of women of a similar age with no personal history of breast carcinoma. Key words: metastatic breast cancer, quality of life, performance status Background Breast cancer is the most common cancer type diagnosed in women worldwide with a 1% increasing incidence (1). According to statistics, 5 to 10% of patients have metastases at diagnosis and 50% of those with an operable breast cancer will experience relapse (2). Despite the fact that we are living in the era of tumor biology and targeted therapy, the average overall survival in metastatic breast cancer (MBC) is 36 months. The end points used in clinical trials are prolongation of life and quality of life. It is important to mention however that a recent meta-analysis of 122 trials noted that still only one third of phase III clinical trials in MBC assess quality of life (QoL)(3).


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QoL is defined as the well-being of individuals and societies, but for cancer patients we should also include the patient’s psychological, functional, emotional and social status. Doctors usually judge patients’ QoL based on our clinical experience, in a subjective way, but in our days an objective assessment regarding QoL is mandatory. Although tumor volume or tumor markers may decrease in response to therapy, this may be associated with an impaired QoL due to treatment toxicities. MBC treatment may entail: hair loss, loss of appetite, nausea and vomiting, weakness and fatigue, lowered resistance to infections, premature menopause, weight gain, mouth soreness, diarrhea, bleeding, lymphedema, depression and anxiety. In this study we analyze the QoL of 5 breast cancer patients with metastases. Data collection To asses QoL we used the Edmonton Symptom Assessment System (ESAS)(Figure1) which we regard as a valid and reliable assessment tool concerning cancer patients’ experience. ESAS integrates the most common symptoms related to metastatic disease and cancer treatment: pain, tiredness, nausea, depression, anxiety, drowsiness, loss of appetite, impaired well-being, and shortness of breath. The severity of each symptom is rated from 0 to 10 on a numerical scale in which 0 means that the symptom is absent and 10 - that it reaches the worst possible severity (4). Figure 1 - Edmonton Symptom Assessment System (ESAS)

None of the patients had filled in the ESAS questionnaire before, but they received clear and easy-to understand instructions regarding the way to use them. In our analysis all evaluated patients had histologically proven MBC, all had received multiple lines of chemotherapy and all of them had filled in evaluation questionnaires based on ESAS score. The score was assessed: before any treatment for MBC was started in our clinic, after the first 3 chemo cycles, and after the last cycle of chemotherapy administrated in our clinic, all correlated with the patient’s performance status, assessed according to the ECOG and Karnofsky scale. Results Patients characteristic are summarized in Table 1.


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Table 1- Patients characteristics

Case 1

NAME C.G.

AGE 47 years old

DG

STAGE IV RIGHT BREAST INVASIVE DUCTAL TYPE CARCINOMA G2 cT4cN3, M1OSS M1LYM – June 2011 M1BRA – October 2013

Tumor biology ER -, PGR -, HER2 positive, KI67 -60%,

Treatment

6 lines of palliative chemotherapy Osteoclast inhibitors - ongoing Targeted therapy for HER2positive - ongoing Radiation therapy – for bone metastasis, brain metastases

Comments

Refused palliative mastectomy Refused hair loss chemotherapy Ulcerated tumor Social active until august 2014 – able to carry out all job requirements even after brain irradiation

Case 2

Name C.M.

Age 63 years old

DG STAGE IA LEFT BREAST DUCTAL CARCINOMA pT1apN0cM0 G2, ER-, PGR -, HER2 positive, KI67 5-10% (1999) – M1BRA- SURGERY, RT M1OSS , M1LYM, M1ADR – June 2011 M1PUL ( august 2013) M1PER ( august 2013)

Tumor biology ER-, PGR -, HER2positive, KI67-15%

Treatment 3 lines of palliative chemotherapy Osteoclast inhibitors – ongoing Targeted therapy for HER2 positive - ongoing RT and surgery for brain metastases

Case 3

Name V. S.

Age: 65 years old

DG: M1PER (BIOPSY - December 2013) STAGE IV LEFT BREAST LOBULAR CARCINOMA. M1OSS, M1LYM

ER+ 80%, PGR + 20%, HER2 - , KI67 60%

Treatment: 2 lines of palliative chemotherapy Osteoclast inhibitors - ongoing Monoclonal antibody VEGFR - ongoing Aromatase inhibitors – ongoing

Median Age (years) 56 (range 47-65)

ECOG (at DG) 1 2 3

20% 60% 20%

Karnofsky (at DG) 50-59 60-69 70-79

40% 20% 40%

Bone metastasis at DG 100%

Visceral metastases at DG 100%

Lines of chemotherapy 2 lines 3 lines >4 lines

40% 40% 20%


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Case 4

Name P.L

Age 55 years old

DG: STAGE IV LEFT BREAST INVASIVE DUCTAL CARCINOMA. PALIATIVE MASTECTOMY G2 pT3pN3 (OCT 2014) .M1HEP. M1LYM. M1OSS. PATHOLOGIC BONE FRACTURE

Tumor Biology: ER + 40%, PGR -, HER2 positive, KI67 30% , LUMINAL B

Treatment: Ongoing of 2nd line palliative chemotherapy Osteoclast inhibitor - ongoing Targeted therapy for HER2positive - ongoing Palliative mastectomy RT – for bone metastases

Case 5

Name D. V.

Age 51 years old

Diagnostic: STAGE IV LEFT BREAST INVASIVE DUCTAL CARCINOMA cT4N2. M1SKY (BIOPSY APR 2014). M1PLE. M1PUL. M1OSS

ER -, PGR -, HER 2positive, KI 67 >14%

Treatment: 3 lines of palliative chemotherapy Targeted therapy for HER2 - ongoing Osteoclast inhibitors - ongoing RT – for bone metastasis Pleurodesis

For our patients we used regimes of less toxic mono and polychemotherapy with targeted agents, HT and osteoclast inhibitors according to metastatic sites and tumor molecular subtypes, using current-day European guidelines, but also taking into account patients’ symptoms and preferences. In Table 2 we present the data of the Karnofsky and ECOG scores. The ESAS score analysis highlighted: - Rapid improvement of performance status (PS) after the first 3 cycles of palliative chemotherapy – the most important issue was the relief of tumor-related symptoms, with decreased pain and good physical status. - The addition of radiation therapy for M1BRA, M1OSS also played an important role by improving significantly patients QoL. The decision to initiate radiotherapy was taken by our multidisciplinary tumor board. MBC is a complex disease, requiring close collaboration of a multidisciplinary team in order to improve survival and QoL. - Despite disease progression, our patients did not experience important changes in their PS, they maintained a score of 0-1 Conclusions In women with MBC, a well conducted treatment should be able to keep a perfect balance between treatment benefits and toxicities. It may achieve a quality of life comparable with that of women of the same age with no personal history of breast cancer. The use of patient’s questionnaires for measuring symptoms improvement is mandatory for a successful MBC management in terms of QoL and disease control.


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Table 2 - The Karnofsky and ECOG scores in 5 cases

CASE 1 CASE 2

Before treatment After 3 cycles Last visit Before treatment After 3 cycles Last visit

Pain 8 0 0 4 0 2

Tiredness 2 0 6 7 1 4

Nausea 0 0 0 0 0 0

Depresion 0 0 7 0 3 0

Anxiety 0 0 0 0 2 0

Drowsiness 0 0 0 2 0 0

Lack of appetite 0 0 7 8 0 0

well being 5 0 6 8 0 0

Dispneea 0 0 0 0 0 0

Other problems 2 0 2 0 0 0

ECOG 1 0 2 2 0 1

Karnofsky 80 100 70 60 100 90

CASE 3 CASE 4

Before treatment After 3 cycles Last visit Before treatment After 3 cycles Last visit

Pain 7 2 1 5 2 0

Tiredness 6 2 2 0 0 6

Nausea 0 0 0 0 0 0

Depresion 2 4 1 0 0 0

Anxiety 0 0 0 0 0 0

Drowsiness 4 0 0 0 0 5

Lack of appetite 9 3 3 0 0 4

well being 7 2 2 5 0 3

Dispneea 0 0 0 0 0 0

Other problems 0 0 0 6 0 0

ECOG 3 1 1 2 1 2

Karnofsky 50 70 80 60 90 70

Case 5

Before treatment After 3 cycles Last visit

Pain 7 4 0

Tiredness 0 5 2

Nausea 0 5 0

Depresion 0 0 0

Anxiety 0 0 0

Drowsiness 3 1 4

Lack of appetite 3 6 0

well being 5 3 0

Dispneea 0 5 0

Other problems 6 0 0

ECOG 2 1 1

Karnofsky 60 80 90


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References

1. Cassidy J, Bissett D, Spence RAJ, Payne M. Oxford Handbook of Oncology 3rd Edition. Oxford: Oxford university Press.2010. 2. Brest cancer treatment.[Available at: http://www.cancer.gov/types/breast/hp/breast-treatment-pdq]. Accessed at 15.03.2015. 3. Metastatic brest cancer.[Available at http://www.medpagetoday.com/resource-center/metastatic-breast-cancer/QoL/a/37067]. Accessed at 5.03.2015. 4. DeVita VT, Lawrence ThS, Rosenberg SA. Devita, Hellman & Rosenberg’s Cancer: Principles & Practice of Oncology. 10th Edition.Lippincott Williams & Wilkins.2014.

Conflict of interest: none Received: 24 May 2015 Accepted: 26 June 2015

http://www.cancer.gov/types/breast/hp/breast-treatment-pdq


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CLINICAL LESSONS

Metastases to the breast - differential diagnosis from primary breast carcinoma: case report Cornelia Nitipir (a,b,c), Bogdan Popescu (b), Andra Cătălina Butolo (b), Cristian Iaciu (b), Alexandru Opriță (b), Răzvan Costin (b), Irina Radu (b), Maria Alexandra Barbu (b)

(a): MD, PhD, senior oncologist, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania (b): MD, oncologist, Elias Emergency University Hospital, Department of Oncology, Bucharest, Romania Corresponding author: Dr Maria Alexandra Barbu, e-mail: [email protected] Abstract Background: Breast cancer is the most common malignancy in women, whereas metastases to the breast from extra mammary malignancies are very rare, accounting for only 0.43% of all malignant breast tumors, with an often poor prognosis: about 80% of patients dying within 1 year of diagnosis. Case report: We present two cases of female patients treated for extra mammary malignancies which developed breast metastases. The first patient, 59 years old, was diagnosed in April 2014 with small cell lung carcinoma, sub diaphragmatic lymph nodes and bone metastases, developed under chemotherapy breast metastasis. This was revealed on a clinical examination in December 2014 and certified in March 2015 by immunohistochemistry as a mammary metastasis of small cell lung carcinoma. The second patient, 45 years old, was diagnosed in February 2012 with sigmoid adenocarcinoma and bilateral ovarian metastases. In January 2015 she performed a digital mammography and a breast tumour was discovered. This was certified in March 2015 by immunohistochemistry as a mammary adenocarcinoma metastasis, intestinal type (colonic). Conclusions: The breast is an uncommon site for metastatic disease. The most frequent source of the metastatic breast lesions are the contralateral breast, lymphomas, melanomas, prostate cancers, lung carcinomas, ovarian carcinomas, renal cell carcinomas, and intestinal tumours. It is important to be acutely aware of both common and uncommon metastases to the breast and to include these appropriately in the differential diagnosis for the optimal patient management. Key words: breast metastases, immunohistochemistry, differential diagnosis Background Metastases to the breast from extra mammary malignancies are very rare, accounting for only 0.43% of all malignant breast tumours (1). The most common primary tumours metastasizing to the breast are lymphomas (17%), melanomas (15%), prostate cancers (12%), lung carcinomas (8%), ovarian carcinomas (8%), renal cell tumours (5%), intestinal tumours (3%) (2,3).


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Most patients have a known diagnosis of extra mammary malignancy at the time the breast metastases are presented. A breast lump may be the first manifestation of malignancy in almost 32% of cases (4). Differential diagnosis between primary breast tumour and metastases to the breast is important in order to decide on clinical management, prognosis and for avoiding unnecessary mutilating breast surgery. The time interval between diagnosis of primary cancer and the appearance of breast metastases ranges from 1 to 5 years (5). The diagnosis is based on the integration of clinical, histological and immunohistochemically examination. Cytomorphologic differentiation between primary and metastatic breast disease is also difficult. Poorly differentiated adenocarcinoma, in particular, is easily confused with ductal carcinoma (6,7). We present two patients with a known diagnosis of extra mammary malignancy, who developed breast metastases under chemotherapy. Cases report The first patient, D.C., 59 years old women, heavy smoker (20 cigarettes per day), was diagnosed in April 2014 with small cell lung carcinoma and sub diaphragmatic lymph node metastases. The immunohistochemistry exam confirmed the diagnosis of small cell lung carcinoma and first line chemotherapy was initiated. In June 2014, IRM of the lumbar spine revealed multiple bone metastasis and Zoledronic acid and external radiation therapy was performed. The patient continued chemotherapy with second line therapy, well tolerated, no significant side effects to be mentioned. In December 2014, on clinical examination, a breast tumour in the left upper outer quadrant was spotted, later confirmed by mammography and ultrasound breast imaging. Left mastectomy was performed and immunohistochemistry examination confirmed the diagnosis of small cell lung carcinoma metastasis, with TTF1, SYNAPTO, CROMO positive, Ki67 positive 80%, ER negative in tumour cells, positive in normal breast tissue and PGR negative in tumour cells, positive in normal breast tissue. In May 2015 the patient was hospitalized in critical condition with acute respiratory failure, chemotherapy was stopped and she received basic supportive care. The second patient, I.C., 45 years old, light smoker (10 cigarettes per day), was diagnosed in February 2012 with stage IV sigmoid cancer (bilateral ovarian metastases). Surgical treatment was performed and the immunohistochemistry exam confirmed the diagnosis. First line chemotherapy was initiated, but in august 2014 whole body computed tomography showed progressive disease: M1HEP M1PUL M1LYM. She started second line chemotherapy, with no significant side effects. In January 2015 the patient presented right breast oedema, erythema and nipple retraction. A mammographic examination was performed and two opacity spikes were described. A biopsy from one of the breast tumours was taken and the immunohistochemistry exam diagnosed metastasis of adenocarcinoma of intestinal type (colonic) with CerbB2 positive >10% in tumour cells, PGR positive 2-3% in tumour cells, Ki67 positive 90% in tumour cells, Ck20, CDX2 positive, Ck7, ER negative. The patient continued treatment with third line chemotherapy and targeted agent therapy, with partial response and no significant side effects. Discussion Breast metastases from extra mammary tumours are rare, a few cases were reported in the literature. Breast is an uncommon site for metastatic disease because it contains large areas of fibrous tissue with a relatively poor blood supply. Like other metastasis, metastases to the breast tend to be rounded and well defined. As opposed to breast cancer, calcification is


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unusual. On mammography, metastatic lesions may manifest as single or multiple masses or as diffuse skin thickening. On ultrasound, metastatic masses tend to have circumscribed margins with low-level internal echoes and, occasionally, posterior acoustic enhancement. Colour Doppler interrogation most often shows increased vascularity. In our cases, besides the rarity of the primary tumour we also have unusual features as nipple retraction and spiculation. Rarely a metastatic lesion to the breast may be spiculated; also metastases do not tend to cause retraction of the skin or nipple. Metastatic lesions are much more likely to be multiple or bilateral than primary cancers and they tend to be found in the subcutaneous fat, whereas primary breast cancers develop in glandular tissue. Axillary lymph nodes are infrequently involved but can occur, particularly in haematological malignancies – none of our patients had axillary lymph nodes involved. Usually metastases to the breast occur several years after the diagnosis of a primary cancer, like the second case reports, but may also occur shortly after primary tumour diagnosis as the first case reports. The occurrence of these breast metastases is related to natural cancer history. Overall, the average age of patients with metastatic breast tumour is usually under 50 years compared with the average age of patients with primary breast cancer (8). Many studies have proved that fine-needle aspiration cytology is the best initial approach to these cases and may provide a definitive diagnosis and avoid unnecessary surgery (6, 7). Immunohistochemistry is essential for a conclusive diagnosis. The treatment includes chemotherapy and, in some cases, radiotherapy. Mastectomy should be avoided but it is sometimes required when the tumour is bulky, deep-seated or painful. Although breast metastases from extra mammary malignancies are infrequent, they generally indicate disseminated metastatic disease and carry a very poor survival rate. Conclusions The breast is an uncommon site for metastatic disease. The most frequent sources of the metastatic breast lesions are the contralateral breast, lymphomas, melanomas, prostate cancers, lung carcinomas, ovarian carcinomas, renal cell carcinomas, and intestinal tumours. An accurate diagnosis is important to avoid unnecessary mutilating surgery especially when patients don’t have a known diagnosis of extra mammary malignancy at the time of the presentation with breast metastases. Patient treatment varies according to the type of primary malignancy diagnosed. Surgical excision of metastatic disease to the breast may be performed for purely palliative indications. References

1. Koch A, Richter-Marot A, Wissler MP, Baratte A, Mathelin C. Mammary metastasis of extramammary cancers: current knowledge and diagnostic difficulties. Gynecol Obstet Fertil. 2013;41(11):653-9. doi: 10.1016/j.gyobfe.2013.09.013. Epub 2013 Oct 30. 2. Bassi F, Gatti G, Mauri E, Ballardini B, De Pas T, Luini A. Breast metastases from cutaneous malignant melanoma. Breast 2004;13(6):533–535. 3. Vizcaino I, Torregrosa A, Higueras V, Morote V, Cremades A, TorresV, Olmos S, Molins C: Metastasis to the breast from extramammary malignancies: a report of four cases and a review of literature. EurRadiol 2001; 11: 1659-1665. 4. Bartella L, Kaye J, Perry N M, Malhotra A, Ev ans D, Ryan D, Wells C, Vinnicombe S J. Metastases to the breast revisited: radiological-histopathological correlation. Clin Radiol 2003 ;58(7):524-31. 5. Lee AH. The histological diagnosis of metastases to the breast from extra mammary malignancies. J Clin Pathol 2007 ;60(12):1333-41. 6. Akcay MN. Metastatic disease in the breast. Breast 2002;11(6):526-8.


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7. Domanski HA: Metastases to the breast from extra mammary neoplasms. A report of six cases with diagnosis by fine needle aspiration cytology. Acta Cytol 1996;40(6):1293-300. 8. Deeley TJ. Secondary deposits in the breast. Br J Cancer 1965;19(4);738-743.

Conflict of interest: none Received: 24 May 2015 Accepted: 26 June 2015


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Palliative chemotherapy and best supportive care for stage IV ovarian cancer patient Irina Radu (b), Maria Alexandra Barbu (b), Bogdan Popescu (b), Silvia Velescu (a,b), Cornelia Nitipir (a,b) (a): MD, PhD, senior oncologist, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania (b): MD, oncologist, Elias Emergency University Hospital, Department of Oncology, Bucharest, Romania Corresponding author: Dr Maria Alexandra Barbu, e-mail: [email protected] Abstract Background: Palliative chemotherapy is the treatment designed for terminal cancer patients to prolong survival and ease symptoms but not cure disease. Best Supportive Care (BSC) is the treatment of choice when cure is not achievable with anticancer agents and involves management of disease-related symptoms. Advanced cancer is generally characterized by loss of moving possibilities, increasing resting time, and gradual loss of interactional capacity. The end of life is defined by: evolution of the malignant disease, depletion of conventional anticancer alternatives and signs of approaching death. Objective: To highlight the importance of delivering palliative chemotherapy lines in order to prolong survival, to control patients’ symptoms at the end of the life and to support the family in accordance to the ethical and legal rules for our country. The aim of the whole treatment applied is to enhance quality of life by the relief of symptoms, once they occur. Methods: We report the case of a 48 year old female patient, diagnosed with stage IV ovarian cancer, who received three chemotherapy lines. She was hospitalized with severe pain (lumbar and right thigh), dyspnea, and anorexia with important nausea. The therapeutic attitude focused on controlling the patient’s symptoms and to provide counseling for the family as well. Conclusion: Best supportive care for cancer patients is a mainstay of palliative care. The goal of palliative care is to achieve the best quality of life for patients and their families. Key words: best supportive care, ovarian cancer, palliative care Case Presentation We describe a 48 year old female patient, former smoker, abstinent for the last 2 years, diagnosed with a left ovarian mass, which achieved debunking surgery with histopathology and immunohistochemistry exam: ovarian papillary serous adenocarcinoma pT3cpN1M1PLE, M1OTH (diaphragm), R2. The residual tissue was a par aortic lymph node. She received twelve cycles of Palictaxel 175 mg/m2 plus Carboplatin AUC 6, qw3, well tolerated. Two months after she finished chemotherapy, PET-CT showed progression with appearance of hepatic, peritoneal, lymphatic, sub diaphragmatic, and supra diaphragmatic metastases.


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The decision was that the patient should receive further chemotherapy so we delivered second line chemotherapy, for platinum resistant patients: Liposomal Doxorubicin, 50 mg/ m2, qw4. The patient received only two cycles because the evaluation of CEA and CA 125 markers showed rapid growing. To confirm the progression, the whole body CT scan showed brain, pleural and lymphatic metastases. Considering that brain MRI scan showed that the metastases were very small, without oedema and the patient had no clinical symptoms, the oncological team concluded that she had to continue with the third line chemotherapy. The decision was to deliver Gemcitabine 1000 mg/m2 d1, d8 and Carboplatin AUC 5 day 1, qw3. After two months of chemotherapy, the patient presented in our department with acute dyspnea at rest, lumbar and right thigh pain and anorexia with important nausea, progressive worsening. The pain intensity was evaluated by the patient on the visual analogue scale at a level of 6-7, with exacerbations up to level 9. The orthopedic surgeon considered that the cause of the pain may be par neoplastic arthritis and recommended pain medication and anti-inflammatory treatment (1). This was performed with iv Dexamethasone 8 mg every 12 hours, alternatively with minor opioid treatment - Tramadol 100mg IV every 6 hours. Due to the persistence of VAS 6-7 pain, major opioid treatment was initiated with Morphine 10 mg sc every 4-6 hours, with good results (2). In order to evaluate the dyspnea and also to detect possible tumors which can determine compression in the abdomen, a whole body CT scan was performed and it showed lymphatic nodules (sub diaphragmatic, supra diaphragmatic and cervical- with compressive vena cava with associated thrombosis), brain, peritoneal, adrenal metastases and pleural effusion associated with lower lobe atelectasis (3). Thoracentesis was performed; the evacuated liquid was hemorrhagic and the cytology evaluation showed malignant cells. After those results, we followed the EAPC 2005 recommendation and we estimate the scores: PaP (palliative prognostic score) (Table 1) and PPI (palliative prognostic index) (Table 2). The results were: 8.5, risk group B, for the first and 6 for the second. The patient received best supportive care for her last days. We controlled the pain, the dyspnea and the nausea. Pain was controlled with Morphine subcutaneous 10 mg at 4-6 hours, with constipation prophylaxis. For the nausea she received Metoclopramid up to 120 mg/day, alternatively with Ondansetron up to 24 mg/day (4). Discussions The majority of ovarian cancer recurrences are in the abdomen. However, some cases relapse as general metastatic disease, with dissemination in vital organs, such as supraclavicular lymph nodes, bone, the lung parenchyma, or the brain. Brain metastases from ovarian cancer are rare and the treatment should associate WBRT, radiosurgery and chemotherapy (5). It is known that in relapse disease, local recurrence or/with disseminate disease, the cells are heterogenic and may have multiple chemotherapy resistance. It is the case of this patient, who had received surgery and three lines of chemotherapy, with no clinical response. After all the therapeutic options failed and the clinical outcome got worse, the patient received palliative care. The goal of such therapy is to improve quality of life for the patient. In our case, the disease progressed rapidly, with distant metastases and chemotherapy resistance, so the patient required palliative care. She died after about one and a half year after being diagnosed.


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Table 1 - The palliative prognostic (PaP) score

Prognostic variable Score

Dyspnoea

Absent 0

Present 1

Anorexia

Absent 0

Present 1,5

Karnofsky performance status

≥50 0

10-40 2,5

Clinician Prediction of Survival

>12 0

11-12 2

7-10 2,5

5-6 4,5

3-4 6

1-2 8,5

Total white blood count

Normal (4800-8500) cell/mm³ 0

High (8501-11 000) cell/mm³ 0,5

Very high (>11 000) cell/mm³ 1,5

Lymphocyte percentage

Normal (20%-40%) 0

Low (12%-19.9%) 1

Very low (0%-11.9%) 2,5

Interpretation of the PaP score

Risk group 30-Day survival Total

probability score

A >70% 0-5.5

B 30-70% 5.6-11

C


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Table 2 - The palliative prognostic index (PPI)

Variable Partial score value

Palliative performance scale (modified Karnofsky)

10-20 4,0

30-50 2,5

≥60 0,0

Oral intake

Severely reduced 2,5

Moderately reduced 1,0

Normal 0

Oedema

Present 1,0

Absent 0,0

Dyspnoea at rest

Present 3,5

Absent 0,0

Delirium

Present 4,0

Absent 0,0

Interpretation of the PPI score

Total score PPV for 6-week NPV for 6-week

survival survival

>4 0,83 0,71

References

1. Hypertrophic Osteoarthropathy. Author: Richa Dhawan. [Available at: http://emedicine.medscape.com/article/333735-overview/ ]. Access of 25.06.2015. 2. Caraceni A, Hanks G, Kaasa S et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncology 2012; 13:e58-68: 3. Guideline for Estimating Length of Survival in Palliative Patients. [Available at: http://palliative.info/resource_material/DecisionMaking.pdf/ ]. Access of 25.06.2015. 4. Stone1 PC, Lund S. Predicting prognosis in patients with advanced cancer. Annals of Oncology 2007;18: 971–976. doi:10.1093/annonc/mdl343 Published online 16 October 2006. 5. Pectasides D. Brain Metastases from Epithelial Ovarian Cancer: A Review of the Literature, The Oncologist March 2006;11(3): 252-260. Conflict of interest: none Received: 24 April 2015 Accepted: 26 May 2015

http://emedicine.medscape.com/article/333735-overview/http://palliative.info/resource_material/DecisionMaking.pdf/


19

NEW PUBLICATIONS

Pregnancy and cancers: from diagnosis to treatments Anca Angela Simionescu, Dragoș Bogdan. Bucharest: Editură Medicală. 2015

As childbearing age increases, the incidence of cancer during pregnancy is rising. The Medical Publishing House has recently published a new Romanian medical book: Anca Simionescu, Dragos Median: Pregnancy and Cancers: from diagnosis to treatments an original multidisciplinary monograph about the diagnosis and management of cancer during pregnancy. The multidisciplinary team included an obstetrician, a medical oncologist, an oncology surgeon, a radiotherapist, a hematologist, a dermatologist, an anesthesiologist, and a psychologist. The team collaboration was important in order to present the best advices about available diagnosis and treatment regiments, the potential risks for both mother and fetus, the prognosis, and the necessity of long-term follow-up. This book is organized to take a pregnant patient through the diagnosis and management of gynecological cancers, hematological malignancy, digestive cancers and melanoma cutaneous and ocular. The text is written by academics who have had personal experience in treating cancer during pregnancy and had reviewed the literature. There is a chapter about genetics and epigenetics of cancer, genetic counseling and testing are also becoming more widely available, especially for people who develop cancer at a young age. Use of chemotherapy and radiotherapy during pregnancy and the potential effects on the fetus are treated in two separate chapters. A chapter about the potential effects of these treatments on the fetus and newborn, the short and long term follow up of the baby was written by a neonatologist with expertise in extreme prematurity. Finally, the psychological impact and the psychosocial stress of a cancer diagnosed during pregnancy was treated separately, included ethical aspects in this field.


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Investigating Barriers to Access and Delivery of Palliative Care for Persons with Dementia in London, Ontario Emily M. Hill. Canada: The University of Western Ontario. 2014 The purpose of this study was to investigate the experiences of staff delivering palliative care to individuals with dementia to determine how care was delivered, to learn which assessment tools were used, and whether policies were affected the delivery of palliative care. Twenty-two staff participants were interviewed. Data were interpreted using phenomenological methodology. Findings yielded three themes: confusion, resource shortages, and communication difficulties. Implications for practice include the clarification of terminology surrounding palliative care, the education of families about dementia and palliative care, better resource management, and a dementia specific model of palliative care. Fruitful areas for future research include how to implement best dementia-specific guidelines, and solutions for more efficient resource use


21

Quality Indicators to Improve Palliative Care in Flanders, Belgium Kathleen Leemans. Development, evaluation and Implementation Strategy. Belgium: Free University Brussels. 2014 This thesis describes the development of a quality indicator set for palliative care and an implementation strategy. The thesis starts with underling the importance of quality indicators. These can facilitate transparency and improvement in care. They also provide important information for patients, caregivers, policy makers as well as researchers. The Council of Europe as well as the World Health Organization (WHO) encourages the development of valid and reliable quality indicators in the field of palliative care. To develop a set of quality indicators three steps were used. Step 1: development of the indicator set. Step 2: feasibility testing and fine-tuning of the indicator set. Step 3: preparing large-scale implementation of the indicator set. Step 1 was started with a systematic review to investigate which quality indicators already existed within the international field of palliative care. Also former systematic reviews were included in the analysis. The literature findings were put into a conceptual framework, containing 9 domains: 1) physical, 2) psychological, social and existential, 3) information, communication, planning and decision making with patients, 4) with family and 5) with other careers, 6) type of care, 7) coordination and continuity, 8) support of friend or family careers and 9) structure of care. This framework was tested by expert consultations, followed by a feasibility study in 9 palliative care settings. Next strategies for implementation were analyzed for different types of palliative care services, using focus group interviews. The ultimate result of this PhD trajectory is a valid and comprehensive indicator set of 84 indicators suitable for quality measurement and improvement by multidisciplinary palliative home care teams, palliative care units, multidisciplinary mobile palliative support teams in hospitals and palliative care reference nurses in care homes and a minimal data set of 31 indicators.


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News During the EAPC World Congress, held in Copenhagen 8-10 May 2015, a poster award was won by a Romanian research group from Iasi. The title of the poster was 'Analysis of Determinants of Impaired Role Functioning Across Prevalent Cancers'. The abstract book of the Copenhagen Congress may be downloaded: http://www.eapc-2015.org/tl_files/eapc15/Downloads/EAPC_2015_Abstract_Book.pdf The next EAPC World Research Congress will be held in Dublin 9-11 June 2016. For more information see: http://www.eapcnet.eu/research2016/
http://www.eapcnet.eu/research2016/

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