eISSN: 2081-2841
ISSN: 1689-832X
Journal of Contemporary Brachytherapy
Current Issue Archive Supplements Articles in Press Journal Information Aims and Scope Editorial Office Editorial Board Register as Author Register as Reviewer Instructions for Authors Abstracting and indexing Subscription Advertising Information Links
SCImago Journal & Country Rank

1/2020
vol. 12
 
Share:
Share:
more
 
 
Educational article

Can brachytherapy be properly considered in the clinical practice? Trilogy project: The vision of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) Interventional Radiotherapy study group

Luca Tagliaferri
,
Andrea Vavassori
,
Valentina Lancellotta
,
Vitaliana De Sanctis
,
Fernando Barbera
,
Vincenzo Fusco
,
Cristiana Vidali
,
Bruno Fionda
,
Giuseppe Colloca
,
Maria Antonietta Gambacorta
,
Cynthia Aristei
,
Renzo Corvò
,
Stefano Maria Magrini

J Contemp Brachytherapy 2020; 12, 1: 84–89
Online publish date: 2020/02/28
Article file
- Can brachytherapy.pdf  [0.27 MB]
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Purpose

Brachytherapy (BT, interventional radiotherapy – IRT) is a kind of radiation therapy, in which the radioactive source is placed nearby or even inside the cancer itself; BT may be used alone or in combination with other therapeutic strategies such as external beam radiation therapy, surgery, or chemotherapy. It may represent a valid alternative to surgery in some circumstances [1] or a necessary complementary step to surgery in other situations [2], therefore it plays a pivotal role in several anatomical areas, or in specific patients who may benefit from the method in a balance between risks and benefits, such as elderly or frail patients [3,4].

Even though this kind of radiation therapy appears effective and valuable, BT has been facing a slow but progressive decline over the past decades in Italy and Europe. However, as experts in the field have highlighted, there are many signs of a renewed interest in BT thanks to new technologies. Even though no European data are available to indicate how much the number of centers offering brachytherapy has fallen, we may have an idea looking at the US National Cancer Database, which showed a decline in the proportion of patients treated with brachytherapy from 62.9% in 2004 to 51.3% in 2012 [5].

The actions supporting BT of the Italian Association Radiotherapy and Clinical Oncology (AIRO) study group on Interventional Radiotherapy are included in the Trilogy project workflow.

To identify the practical and theoretical reasons why BT has faced a slow decline in Italy, a programmatic path divided into three steps like a trilogy was launched. The workflow of our approach is presented in Figure 1.

Fig. 1

Trilogy strategy of the AIRO Interventional Radiotherapy study group

/f/fulltexts/JCB/39777/JCB-12-39777-g001_min.jpg

Steps 1: Survey on clinical “state of the art” in Italy

The Interventional Radiotherapy (Brachytherapy and Intraoperative Radiotherapy) study group of the AIRO conducted a clinical survey among all the Italian centers in order to analyze the use of BT in clinical practice.

In this first paper, a total of 66 questionnaires were obtained (33.5% of all brachytherapy centers in Italy), out of which 48 (74%) from non-academic hospitals, 6 (10%) from academic hospitals, and 12 (16%) from private institutions. Most centers (84%) had only one brachytherapy machine, and 44% did not deliver brachytherapy treatments or delivered less than demanded due the reasons listed in Figure 2 [6].

Fig. 2

Reasons for not using available brachytherapy equipment. Modified from reference [6]

/f/fulltexts/JCB/39777/JCB-12-39777-g002_min.jpg

Steps 2: Survey on educational “state of the art” in Italy

Then, the study group in collaboration with the Gemelli INTErventional Radiotherapy ACtive Teaching School (Gemelli – INTERACTS – Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore), implemented a specific survey aimed at all radiation oncology school directors in Italy to define the main educational training priorities related to BT.

In this second paper, a total of 23 school directors answered the survey. The results evidenced a wide heterogeneity in the learning activities available to trainees in BT across the country. While theoretical knowledge is adequately and homogeneously transmitted to trainees, the types of practice to which they are exposed varies significantly among different schools as reported in Table 1 [7]. Analyzing the different kinds of BT procedures/sites treated, three major groups can be identified according to the survey results:

  1. Available and important for residential training (gynecologic, skin, anus, breast, esophagus, eye).

  2. Important, but not sufficiently available (prostate, sarcoma, head and neck).

  3. Apparently less relevant for residential training (lung, BT in children, and rectal).

Table 1

Brachytherapy (BT) procedures in radiotherapy school. Modified from reference [7]

BT proceduresResponders: available in the academic hospital or in the network
(% of responders to the question)
[% of the total participants to the survey]
Responders: should be part of resident’s training
(% of responders to the question)
[% of the total participants to the survey]
Total number of
responders
Gynecologic21 (95%) [91%]13 (59%) [57%]22
Prostate HDR4 (25%) [17%]15 (94%) [65%]16
Prostate LDR6 (35%) [26%]13 (77%) [57%]17
Skin14 (82%) [61%]9 (53%) [39%]17
Breast8 (62%) [35%]8 (62%) [35%]13
Esophagus9 (69%) [39%]8 (62%) [35%]13
Head and neck8 (57%) [35%]9 (64%) [39%]14
Lung (endobronchial)8 (80%) [35%]5 (50%) [22%]10
Sarcoma9 (53%) [39%]12 (71%) [52%]17
Eye9 (60%) [39%]8 (53%) [35%]15
Rectal7 (54%) [30%]7 (54%) [30%]13
Anus12 (75%) [52%]10 (63%) [43%]16
BT in children6 (60%) [26%]5 (50%) [22%]10

Step 3: Discussion and strategy identification

The third step implied the discussion of the results obtained by the two surveys within the study group, with the definition of a possible strategy to overcome the identified problems. The “Task Force” for the in-depth discussion was composed of 12 people: chair (LT), elected chair (AV), past chair (CA), deputy chairs (CV, VDS), secretary (VL), and board members (FB, VF) of the AIRO Interventional Radiotherapy study group; a member of GIOGER (Italian Group of Geriatric Oncology) (GC), the chair of the scientific commission of the AIRO (RC), the AIRO president (SMM), and member of AIRO committee (MAG).

AIRO Interventional Radiotherapy study group “state of the art” analysis

There is a considerable amount of literature covering the topic of the role of BT in clinical practice; BT can be indicated in exclusive, adjuvant, perioperative setting, but also to deliver a boost. In particular, there is evidence, which has proven that in selected cancers, such as cervical and prostate cancer, BT boost vs. no boost increases overall survival after external beam radiation therapy [8,9,10]. Moreover, there is evidence that the use of intensity modulated or stereotactic radiation therapy as alternatives to BT boost resulted in worse results not only in terms of overall survival, but also with regards to aesthetic results, and function and organ preservation [11,12,13,14]. It is worth to mention that BT plays an important role in treating elderly patients, particularly unfit, frail, or sarcopenic, in which a conservative therapeutic approach may be the best choice [15].

Analyzing the international scenario in terms of cultural background, it becomes clear that there is an adequate attention and consideration towards BT, supported by the presence of dedicated guidelines, with regard to several anatomical sites issued by the main European [16,17,18,19,20,21,22,23,24,25] and American societies [26,27,28]. For this reason, it is sensible to correlate the cultural diffusion of the role and importance of BT at a national level, with its actual diffusion in the clinical practice [29,30,31,32,33,34,35,36,37,38]. In our view, scientific national associations are called to a difficult, but at the same time, fundamental role in supporting and fostering the process of re-discovery of BT through a proper and dedicated vision.

Vision of AIRO Interventional Radiotherapy study group

After having analyzed and discussed the results of the AIRO Interventional Radiotherapy study group surveys, we shared a vision about the emerged issues, so the following strategy was adopted.

Four relevant domains were identified (Table 2):

  1. Clinical practice.

  2. Education.

  3. Research.

  4. Communication.

Table 2

Domains, issues, and relative solutions (accomplished or in progress) proposed according to the defined strategy

DomainIssuesAIRO defined strategy
Clinical practiceInadequate evidence about the role of BT in national clinical guidelines
Inclusion of representatives of IRT study group within the committees for the discussion of national guidelines
Inclusion of IRT study group members in the AGENAS working group for national PDTA
Series of systematic reviews and scientific papers
Promoting synergies with other scientific societies
EducationNeed for an adequate training (especially in residency programs)Consensus conference promotion
Training meeting promotion
University Master promotion
ResearchDifficulties in creating a network to gather strong evidenceSupport to the COBRA project born in the framework of the GEC-ESTRO for a wide international research database
CommunicationDifficulties in communication with other specialists, patients, and also institutional representativesDevelopment of specific printed or web-based booklets for patients
The term “interventional radiotherapy” was introduced in the name of the study group and in routine clinical practice

[i] AIRO – Italian Association of Radiotherapy and Clinical Oncology, AGENAS – National Agency for Regional Sanitary Services, PDTA – Pathway Diagnostic Therapeutic Assistential, COBRA – COnsortium for BRachytherapy data Analysis

Clinical practice

First of all, the working group has fostered the inclusion of BT as a treatment option when clinically indicated, in the frame of national guidelines such as other study groups [39]. To facilitate such goal, representatives of the Interventional Radiotherapy study group were included both in the committee for the discussion of national guidelines and in other AIRO study groups (especially the ones dealing with gynecology, breast, and prostate cancer). Moreover, the members of the study group have been included in the AGENAS (National Agency for Regional Sanitary Services) working group for National Protocols (PDTA, Pathway Diagnostic Therapeutic Assistential).

In the near future, it will be fundamental to include BT within the interdisciplinary guidelines, taking into particular consideration not only cancer patients, but patients who could benefit from these treatments such as frail elderly [40]. For this reason, it has become important to develop synergies with other scientific societies such as GIOGER, SIGG (Italian Society of Geriatrics and Gerontology), and SIOG (International Society of Geriatric Oncology).

A series of systematic reviews and scientific papers were written under the auspices of the AIRO study group and, at the moment, some of them have already been published, whereas others have been submitted [41].

A very interesting point, when considering the potential indications of BT across the different American and European guidelines, is to focus on the level of evidence available.

In fact, for a large number of sites (including prostate, cervix, endometrium, breast, uvea, esophagus), the indications that can be found in the guidelines are actually based on randomized controlled trials (Table 3) [42].

Table 3

Type of study supporting brachytherapy

SiteType of study
CervixRandomized controlled trials
EndometriumRandomized controlled trials
Vulvo-vaginalRetrospective cohort studies
BreastRandomized controlled trials
ProstateRandomized controlled trials
Head and NeckRetrospective cohort studies
UveaRandomized controlled trials
SkinRetrospective cohort studies
EsophagusRandomized controlled trials
AnusRetrospective cohort studies
RectumRetrospective cohort studies
TracheaRandomized controlled trials
Soft tissue sarcomaRandomized controlled trials

Education

Another key point that emerged from our surveys is the need for an improvement of interventional radiotherapy education in Italy, especially to better define and harmonize programs at national level, particularly in practical teaching. For this reason, AIRO supported attendance in experienced centers or national and international courses on specific aspects of BT in order to facilitate the achievement of a satisfying level of BT knowledge among radiation oncologists. Moreover, AIRO endorsed University post-specialty courses (‘second level’ Masters) to allow professionals (already certified in radiation oncology) to acquire more complex BT knowledge. This will facilitate the recruitment of skilled professionals for hospitals’ BT units [43,44].

Research

The role of research in the field of interventional radiotherapy faces the same problems, highlighted in the clinical and educational settings. In fact, one of the greatest issues is the paucity of data due to the relatively small number of patients included in randomized clinical trials. As a possible solution to this problem, there has been a huge effort in creating a national and international network for dedicated research and big data sharing. The study group has thus supported the COBRA (COnsortium for BRachytherapy data Analysis) project born in the framework of the GEC-ESTRO for a wide national research database [45,46,47,48].

Communication

Finally, we believe that difficulties of communication with other specialists, with patients, and also institutional representatives regarding the present modality of the procedures, may represent a further obstacle. Active support to a more accurate knowledge of BT among colleagues and patients should be pursued. However, the ability to address the first three aspects (clinical practice, education, and research) may facilitate a better and more effective communication, especially with the specialists from other oncology branches. A task force was created within the study group for the development of patient specific booklets both paper- and web-based. The term “interventional radiotherapy” was introduced in the name of the study group.

Changing the name allows several advantages, leading to better communication with colleagues and patients because it better explains the effective operational aspects of the technique. According to our view, it results also in better communication with the national institutional representatives, with a consequent smoother procedural and organizational crosstalk, resulting also in a more adequate reimbursement.

Conclusions

Modern interventional radiotherapy can be considered an important tool for the management of cancer patients to be integrated with other therapeutic strategies. The AIRO vision implies that specific strategic interventions must be other specialties in an interdisciplinary setting. We deeply believe that brachytherapy (interventional radiotherapy) is increasingly being considered and in the coming years, we expect more pronounced results.

Disclosure

The authors report no conflict of interest.

References

1 

Buyyounouski MKDavis BJPrestidge BRet al.. A survey of current clinical practice in permanent and temporary prostate brachytherapy: 2010 update. Brachytherapy 2012; 11: 299-305.

2 

Harkenrider MMBlock AMAlektiar KMet al.. American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review. Brachytherapy 2017; 16: 95-108.

3 

Lancellotta VKovács GTagliaferri Let al.. The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin cancer. J Geriatr Oncol 2019; 10: 514-517.

4 

Lancellotta VKovács GTagliaferri Let al.. Age is not a limiting factor in interventional radiotherapy (brachytherapy) for patients with localized cancer. Biomed Res Int 2018; 2018: 2178469.

5 

Fricker J. Brachytherapy: halting the spiral of decline. CancerWorld Magazine 2019; 85: 4-15.

6 

Autorino RVicenzi LTagliaferri Let al.. A national survey of AIRO (Italian Association of Radiation Oncology) brachytherapy (Interventional Radiotherapy) study group. J Contemp Brachytherapy 2018; 10: 254-259.

7 

Tagliaferri LKovács GAristei Cet al.. Current state of interventional radiotherapy (brachytherapy) education in Italy: results of the INTERACTS survey. J Contemp Brachytherapy 2019; 11: 48-53.

8 

Han KMilosevic MFyles Aet al.. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013; 87: 111-119.

9 

Hoskin PJRojas AMBownes PJet al.. Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother Oncol 2012; 103: 217-222.

10 

Gill BSLin JFKrivak TCet al.. National Cancer Data Base analysis of radiation therapy consolidation modality for cervical cancer: the impact of new technological advancements. Int J Radiat Oncol Biol Phys 2014; 90: 1083-1090.

11 

Tagliaferri LPagliara MMFionda Bet al.. Personalized re-treatment strategy for uveal melanoma local recurrences after interventional radiotherapy (brachytherapy): single institution experience and systematic literature review. J Contemp Brachytherapy 2019; 11: 54-60.

12 

Frakulli RGaluppi ACammelli Set al.. Brachytherapy in non melanoma skin cancer of eyelid: a systematic review. J Contemp Brachytherapy 2015; 7: 497-502.

13 

Tagliaferri LManfrida SBarbaro Bet al.. MITHRA–multiparametric MR/CT image adapted brachytherapy (MR/CT-IABT) in anal canal cancer: a feasibility study. J Contemp Brachytherapy 2015; 7: 336-345.

14 

Tagliaferri LLancellotta VFionda Bet al.. Subungual squamous cell carcinoma of the thumb treated by “function sparing approach” using contact radiotherapy (brachytherapy). Turk J Oncol 2019; 34: 283-286.

15 

Colloca GDi Capua BBellieni Aet al.. Muscoloskeletal aging, sarcopenia and cancer. J Geriatr Oncol 2019; 10: 504-509.

16 

Guinot JLRembielak APerez-Calatayud Jet al.. GEC-ESTRO ACROP recommendations in skin brachytherapy. Radiother Oncol 2018; 126: 377-385.

17 

Pieters BRvan der Steen-Banasik ESmits GAet al.. GEC-ESTRO/ACROP recommendations for performing bladder-sparing treatment with brachytherapy for muscle-invasive bladder carcinoma. Radiother Oncol 2017; 122: 340-346.

18 

Kovács GMartinez-Monge RBudrukkar Aet al.. GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update–Improvement by cross sectional imaging based treatment planning and stepping source technology. Radiother Oncol 2017; 122: 248-254.

19 

Strnad VMajor TPolgar Cet al.. ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost–GEC-ESTRO Breast Cancer Working Group practical recommendations. Radiother Oncol 2018; 128: 411-420.

20 

Strnad VHannoun-Levi JMGuinot JLet al.. Recommendations from GEC ESTRO Breast Cancer Working Group (I): Target definition and target delineation for accelerated or boost Partial Breast Irradiation using multicatheter interstitial brachytherapy after breast conserving closed cavity surgery. Radiother Oncol 2015; 115: 342-348.

21 

Major TGutiérrez CGuix Bet al.. Recommendations from GEC ESTRO Breast Cancer Working Group (II): Target defnition and target delineation for accelerated or boost partial breast irradiation using multicatheter interstitial brachytherapy after breast conserving open cavity surgery. Radiother Oncol 2016; 118: 199-204.

22 

Hoskin PJColombo AHenry Aet al.. GEC/ESTRO recommendations on high dose rate afterloading brachytherapy for localised prostate cancer: an update. Radiother Oncol 2013; 107: 325-332.

23 

Haie-Meder CPötter RVan Limbergen Eet al.. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005; 74: 235-245.

24 

Tagliaferri LFionda BBussu Fet al.. Interventional radiotherapy (brachytherapy) for squamous cell carcinoma of the nasal vestibule: a multidisciplinary systematic review. Eur J Dermatol 2019; 29: 417-421.

25 

Pötter RHaie-Meder CVan Limbergen Eet al.. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006; 78: 67-77.

26 

Hepel JTArthur DShaitelman Set al.. American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy. Brachytherapy 2017; 16: 919-928.

27 

Spratt DESoni PDMcLaughlin PWet al.. American Brachytherapy Society Task Group Report: Combination of brachytherapy and external beam radiation for high-risk prostate cancer. Brachytherapy 2017; 16: 1-12.

28 

Nag SErickson BThomadsen Bet al.. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2000; 48: 201-211.

29 

Bandera LLa Face BAntonioli Cet al.. Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis. Eur J Gynaecol Oncol 2014; 35: 121-127.

30 

Fellin GMirri MASantoro Let al.. Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions. Br J Radiol 2016; 89: 20150981.

31 

Barbera FTriggiani LBuglione Met al.. Salvage low dose rate brachytherapy for recurrent prostate cancer after external beam radiotherapy: results from a single institution with focus on toxicity and functional outcomes. Clin Med Insights Oncol 2017; 11: 1179554917738765.

32 

Fozza AGiannelli FBlandino Get al.. Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up. Tumori 2014; 100: 163-168.

33 

Guenzi MGiannelli FAzinwi Cet al.. Accelerated partial breast irradiation via the mammosite catheter: preliminary reports of a single-institution experience. Breast J 2009; 15: 603-609.

34 

Giannelli FChiola IBelgioia Let al.. Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report. J Contemp Brachytherapy 2017; 9: 572-578.

35 

De Sanctis VAgolli LValeriani Met al.. External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial cancer patients: clinical outcomes and toxicity rates. Radiol Med 2013; 118: 311-322.

36 

Autorino RMattiucci GCArdito Fet al.. Radiochemotherapy with gemcitabine in unresectable extrahepatic cholangiocarcinoma: long-term results of a phase ii study. Anticancer Res 2016; 36: 737-740.

37 

Tagliaferri LBussu FFionda Bet al.. Perioperative HDR brachytherapy for reirradiation in head and neck recurrences: single-institution experience and systematic review. Tumori 2017; 103: 516-524.

38 

Tagliaferri LBussu FRigante Met al.. Endoscopy-guided brachytherapy for sinonasal and nasopharyngeal recurrences. Brachytherapy 2015; 14: 419-425.

39 

Mangoni MGobitti CAutorino Ret al.. External beam radiotherapy in thyroid carcinoma: clinical review and recommendations of the AIRO “Radioterapia Metabolica” Group. Tumori 2017; 103: 114-123.

40 

Colloca GCorsonello AMarzetti Eet al.. Treating cancer in older and oldest old patients. Curr Pharm Des 2015; 21: 1699-1705.

41 

Lancellotta VCellini FFionda Bet al.. The role of palliative interventional radiotherapy (brachytherapy) in esophageal cancer: An AIRO (Italian Association of Radiotherapy and Clinical Oncology) systematic review focused on dysphagia-free survival. Brachytherapy 2019; pii: S1538-4721(19)30583-5.

42 

Chargari CDeutsch EBlanchard Pet al.. Brachytherapy: An overview for clinicians. CA Cancer J Clin 2019; 69: 386-401.

43 

Kovács GTagliaferri LValentini V. Is an Interventional Oncology Center an advantage in the service of cancer patients or in the education? The Gemelli Hospital and INTERACTS experience. J Contemp Brachytherapy 2017; 9: 497-498.

44 

Tagliaferri LPagliara MMBoldrini Let al.. INTERACTS (INTErventional Radiotherapy ACtive Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) procedures. J Contemp Brachytherapy 2017; 9: 287-295.

45 

Tagliaferri LGobitti CColloca GFet al.. A new standardized data collection system for interdisciplinary thyroid cancer management: Thyroid COBRA. Eur J Intern Med 2018; 53: 73-78.

46 

Tagliaferri LBudrukkar ALenkowicz Jet al.. ENT COBRA ONTOLOGY: the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy). J Contemp Brachytherapy 2018; 10: 260-266.

47 

Meldolesi Evan Soest JAlitto ARet al.. VATE: VAlidation of high TEchnology based on large database analysis by learning machine. Colorectal Cancer 2014; 3: 435-450.

48 

Tagliaferri LKovács GAutorino Ret al.. ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy). J Contemp Brachytherapy 2016; 8: 336-343.

Copyright: © 2020 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe