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"Latar Belakang: Belum ada kesepakatan global penanda deteksi dini kejadian metastasis tulang pada pasien kanker payudara. Penelitian ini bertujuan menganalisis hubungan ekspresi tinggi penanda biologi CXCR4, IL11-RA, TFF1 dan MLF1P, klinikopatologi dan profil ekspresi genetik mRNA sebagai penanda peningkatan kejadian metastasis tulang pada pasien kanker payudara stadium lanjut.Metode: Metode penelitian adalah potong lintang komparatif. Analisis dilakukan pada, total 92 pasien kanker payudara, terdiri atas 46 pasien metastasis tulang dan 46 pasien dengan metastasis nontulang. Analisis microarray, dilakukan pada 81 sampel FFPE dari 81 pasien yang didapat. Data dikumpulkan melalui rekam medis, pemeriksaan imunohistokimia, dan microarray dengan nanoString nCounter^TM.Hasil: Diperoleh IL11-RA dengan cut-off ≥ 103,5 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 3,803 (95 % interval kepercayaan [IK], 1,375-10,581), p = 0,010, dan MLF1P dengan cut-off ≥ 83,0 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 2,784 (95% IK, 1,009-7,681), p = 0,048. Status ER+ menunjukkan peningkatan kejadian metastasis tulang, dengan OR 7,640 (95 % IK, 2,599-22,459), p < 0,000. AUC gabungan IL-11RA, MLF1P dan ER+, mempunyai ketepatan hampir 80%, (meningkat dibandingkan AUC masing-masing secara terpisah), untuk membedakan dan menjelaskan kejadian metastasis tulang, pada kanker payudara stadium lanjut.  Pada kanker payudara metastasis tulang dengan organ lain (MT+), diperoleh panel 22-gen, dengan 13 gen: upregulated dan 9 gen downregulated ; pada metastasis hanya tulang (MT) diperoleh panel 17-gen dengan 13 ekspresi gen upregulated dan 4 ekspresi gen downregulated . Kedua panel memberikan hasil berbeda bermakna pengelompokan unsupervised, terhadap metastasis nontulang. Analisis berdasarkan diagnosis dua kelompok metastasis tulang, ekspresi ESR1 merupakan gen dengan perubahan ekspresi tertinggi, dan berdasarkan proporsinya, didapatkan 3 gen pada MT+, dan 8 gen pada MT, termasuk di antaranya ESR1, GATA3 dan MLPH/ ANXA9, yang meningkatkan kemungkinan kejadian metastasis tulang. Simpulan: IL11-RA, MLF1P dan ER+, merupakan variabel yang berhubungan dengan peningkatan kejadian metastasis tulang pasien kanker payudara stadium lanjut. Diperoleh panel 22 ekspresi gen pada MT+, dan panel 17 ekspresi gen untuk MT yang berekspresi berbeda bermakna dibanding metastasis nontulang. Analisis berdasarkan diagnosis dua kelompok metastasis tulang, diperoleh 3 gen pada MT+, dan 8 gen pada MT, yang diusulkan menjadi kandidat training set selanjutnya.

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Background: The aim of this research was to analyze the correlation between high expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, clinicopathology and genetic expression profiles (mRNA) in advanced breast cancer patients with bone metastatic.Methods: The methods used were comparative cross-sectional. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. In microarray test, a total of 81 FFPE samples from 81 patients were used.Results: IL11-RA with cut-off ≥ 103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581), p = 0.010, MLF1P with cut-off ≥ 83.0 OR 2.784 (95% CI, 1.009-7.681), p = 0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459), p < 0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80 % to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients. The results of genetic expression profiles showed that the 22 genes expressions were significantly different between bone metastatic with other organs patients (MT+), and non bone metastatic patients, which consisted of 13 genes expression upregulated and 9 genes expression downregulated, while subject with only bone metastasis (MT), showed that 17 genes expressions were significantly different, consisting of 13 genes expression upregulated and 4 genes expressions downregulated. Based on diagnosis both types of bone metastasis, the ESR1 gene was the highest expressed, and base on proportion distribution there were 3 genes in MT+, and 8 genes in MT, including ESR1, GATA3, and MLPH/ ANXA9, associated with increasing bone metastasis incidences, which can be the next candidate for the training set.Conclusion: IL11-RA, MLF1P, and ER+ were the variables that were associated with increasing bone metastasis incidence. There was a panel of 22 genes expression in bone metastasis and a panel of 17 genes expression for only bone metastasis that had significantly different expressions, compared to non-bone metastastasis. Based on diagnosis both types of bone metastasis, there is 3 genes in MT+, and 8 genes in MT, that can be the next candidate of training set."

"[ABSTRAKVolumetric Modulation Arc Therapy (VMAT) merupakan salah satu modalitas untukpengobatan kanker yang mempunyai beberapa teknik penyinaran. Dalam penelitiandilakukan karakteristik dosimetri dan dosimetri invivo menggunakan TLD-100 roddan film gafchromic EBT3 dengan teknik full arc dan half arc VMAT pada fantomrando kasus kanker parotid kiri dan kanker paru ? paru apeks kiri yang masing -masing memiliki empat target dengan volume yang berbeda. Evaluasi yang dilakukanmeliputi parameter penyinaran, Homogeneity Index (HI), Conformity Index (CI) dandeviasi pengukuran dosis menggunakan TLD dan film dengan TPS. Total MU yangdigunakan dan waktu penyinaran, teknik full arc lebih besar dibandingkan teknik halfarc. Selain itu, laju dosis yang diperlukan untuk VMAT teknik full-arc lebih rendahdibandingkan dengan teknik half arc,Teknik full arc lebih homogen dan konformitasdibandingkan pada teknik half arc. Pada pengukuran dosis titik menunjukkan bahwateknik full-arc dan half-arc mempunyai nilai deviasi yang tidak besar, danpenggunaan TLD lebih efektif jika dibandingkan dengan film, dimana rata ? ratadeviasi dosis penggunaan TLD antara 3,79 ? 5,76 % untuk target dan 6,38 ? 9,3 %untuk organ at risk (OAR), dan pada penggunaan film antara 5,69 ? 11,85 % untuktarget dan 34,40 ? 215,76 % untuk OAR.

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ABSTRACT

Volumetric Modulation Arc Therapy (VMAT) is one of the modalities for cancer

treatment that have some technique. This study conducted, dosimetry

characterizations and determination dose by TLD and gafchromic EBT3 film with

full arc and half arc VMAT technique at rando phantom for left parotid cancer and

left apex lung cancer case, which each case have four target different volumes.

Evaluation was conducted on the irradiation parameters, homogeneity index (HI),

Conformity Index (CI) and the deviation of dose measurement using TLD and films

with TPS. On VMAT, the total MU which used and the total of delivery treatment

time, on full arc technique is greater than the half arc technique. Results of the study

the dose rate necessary for VMAT technique of full arc lower than the technique of

half arc, VMAT technique full arc more homogeneous and conformity compared to

the technique of half arc. The measurement of the dose point of use TLD is more

effective than the use of the film, where deviations dose average using TLD between

3.79 to 5.76 % for target and 6.36 to 9.3 % for organ at risk (OAR), and the use of

film between 5.69 to 11.85 % for target and 34.4 to 215.76 % for OAR.;Volumetric Modulation Arc Therapy (VMAT) is one of the modalities for cancer

treatment that have some technique. This study conducted, dosimetry

characterizations and determination dose by TLD and gafchromic EBT3 film with

full arc and half arc VMAT technique at rando phantom for left parotid cancer and

left apex lung cancer case, which each case have four target different volumes.

Evaluation was conducted on the irradiation parameters, homogeneity index (HI),

Conformity Index (CI) and the deviation of dose measurement using TLD and films

with TPS. On VMAT, the total MU which used and the total of delivery treatment

time, on full arc technique is greater than the half arc technique. Results of the study

the dose rate necessary for VMAT technique of full arc lower than the technique of

half arc, VMAT technique full arc more homogeneous and conformity compared to

the technique of half arc. The measurement of the dose point of use TLD is more

effective than the use of the film, where deviations dose average using TLD between

3.79 to 5.76 % for target and 6.36 to 9.3 % for organ at risk (OAR), and the use of

film between 5.69 to 11.85 % for target and 34.4 to 215.76 % for OAR., Volumetric Modulation Arc Therapy (VMAT) is one of the modalities for cancer

treatment that have some technique. This study conducted, dosimetry

characterizations and determination dose by TLD and gafchromic EBT3 film with

full arc and half arc VMAT technique at rando phantom for left parotid cancer and

left apex lung cancer case, which each case have four target different volumes.

Evaluation was conducted on the irradiation parameters, homogeneity index (HI),

Conformity Index (CI) and the deviation of dose measurement using TLD and films

with TPS. On VMAT, the total MU which used and the total of delivery treatment

time, on full arc technique is greater than the half arc technique. Results of the study

the dose rate necessary for VMAT technique of full arc lower than the technique of

half arc, VMAT technique full arc more homogeneous and conformity compared to

the technique of half arc. The measurement of the dose point of use TLD is more

effective than the use of the film, where deviations dose average using TLD between

3.79 to 5.76 % for target and 6.36 to 9.3 % for organ at risk (OAR), and the use of

film between 5.69 to 11.85 % for target and 34.4 to 215.76 % for OAR.]"