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1.
Nanoscale ; 13(40): 17077-17092, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34622906

RESUMO

Advanced inoperable triple-negative breast cancer (TNBC) comprises aggressive tumors with a modest pathological response to neoadjuvant chemotherapy. The concomitant use of chemoradiotherapy improves the pathological response rates. However, the dose-dependent systemic toxicity of clinical radiosensitizers with poor circulation half-life and limited passive bioavailability limits their clinical utility. We address these challenges by rationally designing a stealth and tumor microenvironment responsive nano-conjugate platform for the ultrasound-mediated on-demand spatio-temporal delivery of plant flavonoid curcumin as a combinatorial regimen with clinically approved paclitaxel for the neoadjuvant chemoradiotherapy of locally advanced triple-negative breast cancer (TNBC). Interestingly, the focused application of ultrasound at the orthotopic TNBC xenograft of NOD-SCID mice facilitated the immediate infiltration of nano-conjugates at the tumor interstitium, and conferred in vivo safety over marketed paclitaxel formulation. In addition, curcumin significantly potentiated the in vivo chemoradiotherapeutic efficacy of paclitaxel upon loading into nano-conjugates. This gets further enhanced by the concurrent pulse of ultrasound, as confirmed by PET-CT imaging, along with a significant improvement in the mice survival. The quadrapeutic apoptotic effect by the combination of paclitaxel, curcumin, radiation, and ultrasound, along with a reduction in the tumor microvessel density and cell proliferation marker, confers the broad chemo-radiotherapeutic potential of this regimen for radio-responsive solid tumors, as well as metastatic niches.


Assuntos
Medicina de Precisão , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral
2.
Breast ; 60: 177-184, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34655887

RESUMO

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

3.
J Contemp Brachytherapy ; 13(4): 387-394, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34484352

RESUMO

Purpose: The aim of this study was to compare patient-reported quality of life (QOL) scores after accelerated partial breast irradiation (APBI) using interstitial brachytherapy vs. external beam whole breast radiotherapy (WBRT) for breast cancer. Material and methods: Women with breast cancer treated with WBRT or APBI after breast conservation surgery were enrolled in this prospective study. Single cross-sectional QOL assessment was performed using EORTC QLQ-C30 and BR-23 questionnaires. Patients treated with APBI were propensity-score matched to similar cohort of patients treated with WBRT. QOL scores were analyzed for the entire unmatched cohort and compared between the two matched cohorts using Student's two-tailed t-test. P-value of < 0.05 was considered statistically significant, and a 10-point difference between mean scores was considered clinically meaningful. Results: A total of 64 APBI patients were matched with 99 WBRT patients out of the entire study cohort of 320 cases. QOL scores for functional scales of QLQ-C30 were similar between the two groups for both matched and unmatched cohorts, while symptom scores of QLQ-C30 did not show any clinically significant difference. Functional scales of BR-23 did not show any clinical or statistically significant difference. Among symptom scales of BR-23, scores were similar for APBI and WBRT groups except for a worse score of "upset by hair loss" sub-scale in the brachytherapy group of the matched cohort (51.9 vs. 22.7, p = 0.006). Conclusions: Patients undergoing APBI reported similar QOL compared to WBRT when matched for various factors.

4.
JCO Glob Oncol ; 7: 464-473, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33822644

RESUMO

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.


Assuntos
COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Radioterapia (Especialidade)/estatística & dados numéricos , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários , Adulto , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/prevenção & controle , Transtornos de Ansiedade/psicologia , Bangladesh/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Estudos Transversais , Depressão/epidemiologia , Depressão/prevenção & controle , Depressão/psicologia , Feminino , Pessoal de Saúde/psicologia , Humanos , Índia/epidemiologia , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Pandemias , Radioterapia (Especialidade)/métodos , SARS-CoV-2/fisiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
5.
Asian Pac J Cancer Prev ; 22(3): 793-800, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773543

RESUMO

BACKGROUND: Cancer treatment during nationwide lockdown due to the COVID-19 pandemic has posed several challenges in the delivery of cancer care and carries tremendous potential sequel of impoverishing the households. This study aims to examine the economic distress faced by breast cancer patients receiving treatment at Tata Memorial Center (TMC) Mumbai, India during the nationwide lockdown initiated in March 2020 following the outbreak of COVID-19. METHODS: A total of 138 non-metastatic breast cancer patients who were accrued in this study at TMC before imposing of lockdown, and their treatment was impacted because of the COVID-19 outbreak, were interviewed. Telephonic interviews were conducted using a structured schedule which contained information on household and demographic characteristics of the patients, knowledge about COVID-19, their daily expenditure for treatment, difficulties faced during lockdown and how they met expenditures. Descriptive statistics and logistic regression were used in the analyses. RESULTS: The average monthly expenditure of cancer patients had increased by 32% during the COVID-19 period while the mean monthly household income was reduced by a quarter. More than two-thirds of the patients had no income during the lockdown. More than half of the patients met their expenditure by borrowing money, 30% of the patients used their savings, 28% got charity and 25% used household income. About 81% of the patients had reported shortage of money, 32%  reported shortage of food and 28% reported shortage of medicine. The distress financing was significantly higher among patients receiving treatment in Mumbai compared to those receiving treatment at their native cities (67% vs. 46%), patients under 40 years of age, illiterate, currently married, Muslim and staying at a rented house. CONCLUSION: The incremental expenditure coupled with reduced or no income due to the closure of economic activities in the country imposed severe financial stress on breast cancer patients.


Assuntos
Neoplasias da Mama/economia , COVID-19 , Efeitos Psicossociais da Doença , Estresse Financeiro , Financiamento Pessoal , Gastos em Saúde , Adulto , Fatores Etários , Neoplasias da Mama/terapia , Estudos de Coortes , Controle de Doenças Transmissíveis , Feminino , Geografia , Humanos , Renda , Índia , Alfabetização , Estado Civil , Pessoa de Meia-Idade , Religião , SARS-CoV-2
6.
Indian J Cancer ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33753616

RESUMO

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

7.
Breast ; 56: 88-95, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640524

RESUMO

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.


Assuntos
Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Idade Gestacional , Humanos , Incidência , Índia/epidemiologia , Mastectomia , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Prognóstico , Receptor ErbB-2 , Sistema de Registros , Análise de Sobrevida
8.
J Plast Reconstr Aesthet Surg ; 74(9): 2176-2183, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33478895

RESUMO

Plastic surgical principles are incorporated with breast conservation surgery (BCS) for cancer to improve aesthetic outcomes. In developing countries, average tumour size is larger at presentation resulting in larger resections often, including overlying skin. LD flap has been the workhorse of partial breast reconstruction. We present an easy and effective alternative to LD flap for carefully selected cases of outer quadrant breast tumours. We report 41 cases of local transposition flap from the lateral chest wall for oncoplastic restoration post BCS, performed between January 2016 and February 2020, at our institution. The median age was 49 years (28-63). Twenty-six patients underwent upfront surgery and 15 after neoadjuvant chemotherapy (NACT). The average pathological tumour size was 2.9 cm (median 2.7 and range 1.1-6) and 1.5 cm (median 1.8 and range 0-3.5) for upfront and post-NACT groups, respectively. The median volume of the resected specimen was 277.8 ml and 253.2 ml for upfront and post-NACT groups, respectively. Three patients (7.5%) had a microscopic positive margin requiring margin revision. Three (7.5%) patients had post-operative minor wound complications and were managed conservatively. At a median follow-up of 14 months (1-36), only 2/19 (10.5%) patients had clinical fat necrosis. Local transposition flap from the lateral chest wall based on dermal and subdermal plexus, carefully designed in selected patients, can be used effectively for the reconstruction of outer quadrant breast defects. It is easy to learn, offers good cosmetic outcome, avoids the morbidity and time of LD flap and saves LD flap for future use.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Retalhos Cirúrgicos , Adulto , Estética , Feminino , Sobrevivência de Enxerto , Humanos , Pessoa de Meia-Idade
9.
Brachytherapy ; 20(1): 155-162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32888852

RESUMO

PURPOSE: The purpose of the study was to report dosimetric differences for breast brachytherapy plans optimized for clinical target volume (CTV) generated using conventional isotropic expansion of tumor bed volume (TBV) and Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) recommendations to expand the TBV anisotropically to achieve a total safety margin of 2 cm (resection margin size + added safety margin). METHODS: Institutional records of 100 patients who underwent accelerated partial breast irradiation using multicatheter interstitial brachytherapy from May 2015 to March 2020 were reviewed retrospectively. Two sets of CT-based plans were made, one with 1-cm isotropic margins around the tumor bed (CTV_ISO) and the other with anisotropic margins (CTV_GEC). Plans were evaluated and compared using the American Brachytherapy Society and GEC-ESTRO guidelines. RESULTS: The median TBV was 36.97 cc. The median margin widths were as follows: anterior 1.2, posterior 1.0, superior 1.0, inferior 0.9, medial 1.2, and lateral 1.2 cm. The mean tumor bed coverage index was 0.94; 0.93 [p.066], the CTV coverage index 0.86; 0.84 [p 0.001], the dose homogeneity index (DHI) 0.77; 0.75 [p < 0.001] and the conformity index 0.66; 0.64 [p < 0.001] in CTV_ISO and CTV_GEC plans, respectively. In smaller volume implants (TBV< 35 cc), the DHI was 0.76; 0.75 [p 0.008] and the conformity index was 0.66; 0.62 [p < 0.001], whereas in larger volumes >35 cc, the CTV coverage index was 0.86; 0.84 [p 0.003] and the DHI 0.78; 0.76 [p 0.001] in CTV_ISO and CTV_GEC plans, respectively. CONCLUSIONS: In this cohort of patients who underwent accelerated partial breast irradiation, plans with anisotropic margins had lower conformity, the impact of which was predominantly seen in smaller implants. Rest of the dosimetric constraints were achieved in both the plans as per the American Brachytherapy Society and GEC-ESTRO guidelines.


Assuntos
Braquiterapia , Braquiterapia/métodos , Mama , Humanos , Margens de Excisão , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos
10.
Brachytherapy ; 19(5): 694-699, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684407

RESUMO

PURPOSE: The purpose of this study was to define dose constraints for catheter insertion sites to minimize probability of prominent post-therapy skin marks after interstitial breast brachytherapy. METHODS AND MATERIALS: Forty patients who had undergone interstitial breast brachytherapy were studied at followup at least 2 years after the procedure. Their implant marks were compared with background skin and areola and scored as Gr0 = invisible (same color as surrounding skin), Gr1 = darker than surrounding skin but lighter than areola or hypopigmentation, and Gr2 = same color as areola or darker. Highest point doses received in each plane of implant and their corresponding closest distances from clinical target volume, 85% isodose, and closest catheter dwell point were used for analysis. A logistic regression was performed to ascertain effects of various dosimetric parameters on the probability of Gr2 marks. Receiver operating characteristic curve was generated to derive cutoffs. RESULTS: A total of 280 dose points were studied. Median values for various parameters were 1.4 Gy (0.24-3.74) for Dose max and 1.6 cm, 1.5 cm, and 1.0 cm for Dist CTV min, Dist Iso min, and Dist Dwell min, respectively. On logistic regression, increasing Dose max alone was associated with an increased likelihood of developing Gr2 marks. Each unit increase of Dose max increased probability of development of Gr2 skin marks by 5.0% (2.391-10.328). Receiver operating characteristic analysis also showed greatest odd ratio (8.0), sensitivity (74.8%), and specificity (73%) for Dose max. CONCLUSIONS: It seems prudent to restrict dose to catheter insertion sites for better cosmesis.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Hiperpigmentação/epidemiologia , Hipopigmentação/epidemiologia , Mastectomia Segmentar , Lesões por Radiação/epidemiologia , Dosagem Radioterapêutica , Idoso , Mama , Cateteres , Feminino , Humanos , Pessoa de Meia-Idade , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante/métodos , Pele , Pigmentação da Pele
11.
Brachytherapy ; 19(3): 337-347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32359677

RESUMO

PURPOSE: The purpose of this study is to evaluate long-term clinical outcomes of women treated with accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy (MIB-APBI) with risk groups defined by Groupe Européen de Curie-thérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO), American Society for Radiation Oncology (ASTRO), updated ASTRO, and American Brachytherapy Society (ABS) guidelines and to elucidate the most appropriate guideline that could differentiate outcomes among its risk groups. METHODS AND MATERIALS: Two hundred forty women underwent MIB-APBI during July 2000 to March 2013. Comparisons of long-term clinical outcomes (local control [LC], disease-free survival [DFS], cause-specific survival [CSS], and overall survival [OAS]) stratified by the risk groups proposed by the aforementioned patient selection guidelines were carried out on a prospectively maintained database. RESULTS: At a median follow-up of 114 months, 10-year LC, DFS, and OAS were 90%, 81%, and 83.5%, respectively, for the entire group. There was no statistically significant difference in the LC rates for risk groups by ESTRO, ASTRO, updated ASTRO and ABS guidelines. The 10-year DFS and OAS for GEC-ESTRO low-, intermediate-, and high-risk group was 75%, 88%, and 60% (p = 0.02) and 86%, 93%, and 62% (p = 0.001), respectively. Ten-year DFS and OAS in the ABS 2018-acceptable and ABS 2018-unacceptable group were 78% and 67% (p = 0.01) and 88% and 69% (p = 0.001), respectively. No significant difference in any of the outcomes was observed with risk groups suggested by ASTRO or updated ASTRO consensus guidelines. CONCLUSIONS: None of the current patient selection guidelines for APBI could differentiate LC (main APBI endpoint) among its risk groups, whereas GEC-ESTRO and ABS guideline could differentiate DFS and OAS.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Adulto , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Radioterapia (Especialidade) , Fatores de Risco , Taxa de Sobrevida , Estados Unidos
12.
Indian J Cancer ; 57(2): 144-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32445317

RESUMO

A histopathology report offers important prognostic and predictive information that helps plan systemic therapy in breast cancer. However, in many cases a pathologist fails to provide relevant information chiefly due to the lack of awareness of the impact of these parameters in clinical decision-making. This review seeks to put forth common practice points in grossing and reporting of specimens harboring breast cancer with focus on latest revisions in the same. Just as it is important to document tumor size, tumor type, margins, estrogen receptor/progesterone receptor, and human epidermal growth factor (ER/PR/HER2) in breast cancer, we need to also focus on sentinel node grossing, nodal burden, size of nodal metastasis, and extranodal extension. In parallel, increasing number of patients are getting neoadjuvant chemotherapy in breast cancer and points in grossing and reporting of such specimens are also alluded to. This article will serve as reference guide to pathologists on what we do and why we do the same.


Assuntos
Neoplasias da Mama/epidemiologia , Notificação de Doenças/métodos , Medicina Baseada em Evidências/métodos , Feminino , Humanos
13.
J Contemp Brachytherapy ; 12(2): 160-165, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395140

RESUMO

Purpose: The aim of this study was to propose an index for evaluating dosimetric impact of inter-observer target delineation variability in brachytherapy. Material and methods: The coverage with dosimetric concordance index (CDCI) is expressed as CDCIcommon and CDCIpair. The CDCIcommon is the mean coverage of target volume with common volume irradiated by prescription dose among all observers and represents the condition of worst target coverage. CDCIpair is the generalized form of CDCI, which is mean target coverage with common prescription volume obtained between all possible pairs of observers and represents more realistic coverage of target with dosimetric concordance. The index was used to evaluate the dosimetric impact of target delineation variability in optimized conformal plans on target volumes of five radiation oncologists for twenty patients of multi-catheter interstitial partial breast brachytherapy. Results: The mean decline of 5.6 ±3.2% and 11.3 ±5.7% in CDCIpair and CDCIcommon, respectively, was observed comparing to coverage index (CI) of target volume in all patients due to inter-observer target variability. CDCIcommon and CDCIpair were found to have significant linear correlation (r = 0.964, p < 0.000). The difference between CDC and CI increased with the mean relative target volume among observers. Significant correlation (r = 0.962, p < 0.000) was also noted for the difference (Δ) in CDCIcommon and CDCIpair with CI of target volume. Conclusions: The recommended indices and difference between the dosimetric coverage of target volume (CI) with CDCI (ΔCDCI) can be used for evaluating dosimetric impact of the inter-observer target delineation variability.

14.
Breast Cancer ; 27(2): 206-212, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31512161

RESUMO

BACKGROUND: To compare the early cosmetic outcomes after whole breast radiotherapy (WBRT) and accelerated partial breast irradiation (APBI) by various cosmetic assessment methods. MATERIALS/METHODS: APBI was delivered using multiplane interstitial brachytherapy as per standard guidelines. Majority of women in WBRT cohort received hypo-fractionated external beam radiotherapy using bitangential portals and mega-voltage photons along with sequential boost to the tumor bed. Single cross-sectional assessment (18-36 months post-treatment completion) of the breast cosmesis was done by RO, SO and the patient using the modified Harvard scale and by photographic assessment using the BCCT.core software. The two cohorts were propensity score-matched using menopausal status, size of surgical cavity, size of tumor in greatest dimension, median number of lymph nodes dissected, treatment with adjuvant chemotherapy and treatment with hormonal therapy. RESULTS: A total of 64 APBI patients were matched with 99 WBRT patients of the entire cohort of 320. At a median follow-up of 25 months, cosmetic results were significantly better for APBI as compared to WBRT cohort by all methods of evaluation (excellent/good: RO:75% vs 38.4%, p = 0.0001; SO: 54.7% vs 37.4%, p = 0.009; patient: 87.5% vs 58.6%, p = 0.001 and BCCT: 73.4% vs 51.6%, p = 0.001). Individual parameters that were significantly better in APBI cohort included size and shape of breast as well as location and shape of NAC. Better results for individual BCCT parameters (pLBC, pBRE, pBAD) were also seen. CONCLUSIONS: Overall cosmetic outcomes as well as individual subdomains are significantly better with APBI as compared to WBRT by all methods of assessment of cosmesis when matched for various factors.


Assuntos
Neoplasias da Mama/radioterapia , Satisfação do Paciente , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Implantes de Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Estudos Transversais , Feminino , Humanos , Mastectomia Segmentar , Análise por Pareamento , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Hipofracionamento da Dose de Radiação , Radioterapia/efeitos adversos
15.
Front Cell Dev Biol ; 8: 597673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33490064

RESUMO

Substantial number of breast cancer (BC) patients undergoing radiation therapy (RT) develop local recurrence over time. During RT therapy, cells can gradually acquire resistance implying adaptive radioresistance. Here we probe the mechanisms underlying this acquired resistance by first establishing radioresistant lines using ZR-75-1 and MCF-7 BC cells through repeated exposure to sub-lethal fractionated dose of 2Gy up to 15 fractions. Radioresistance was found to be associated with increased cancer stem cells (CSCs), and elevated EpCAM expression in the cell population. A retrospective analysis of TCGA dataset indicated positive correlation of high EpCAM expression with poor response to RT. Intriguingly, elevated EpCAM expression in the radioresistant CSCs raise the bigger question of how this biomarker expression contributes during radiation treatment in BC. Thereafter, we establish EpCAM overexpressing ZR-75-1 cells (ZR-75-1EpCAM), which conferred radioresistance, increased stemness through enhanced AKT activation and induced a hybrid epithelial/mesenchymal phenotype with enhanced contractility and invasiveness. In line with these observations, orthotopic implantation of ZR-75-1EpCAM cells exhibited faster growth, lesser sensitivity to radiation therapy and increased lung metastasis than baseline ZR-75-1 cells in mice. In summary, this study shows that similar to radioresistant BC cells, EpCAM overexpressing cells show high degree of plasticity and heterogeneity which ultimately induces radioresistant and metastatic behavior of cancer cells, thus aggravating the disease condition.

16.
J Contemp Brachytherapy ; 11(3): 207-214, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31435427

RESUMO

Purpose: We evaluated agreement between subjective and objective methods of cosmesis scoring in an accelerated partial breast irradiation (APBI) cohort. Material and methods: Consecutive women treated with APBI using interstitial brachytherapy reported for clinical follow-up every 6 months. Single cross-sectional assessment of the breast cosmesis was done by a radiation oncologist (subjective method) using Harvard scale and by photographic assessment using BCCT.core (Breast Cancer Conservative Treatment. Cosmetic results, version 3.1) software (objective method) at 18-36 months post-APBI. The agreement between subjective and objective methods for the overall score as well as individual subjective/objective subdomains was computed using kappa statistics. ANOVA was used to test the correlation between objective indices and subjective subdomains. Results: The agreement between the subjective (physician) and objective assessment was good with a kappa of 0.673. Overall, 77 (98.7%) patients were satisfied with the overall outcomes of breast conservation therapy. The kappa agreement between physician and patient scoring was 0.457 (95% CI: 0.240-0.674). Among the subjective subdomains, location of the nipple areola complex (NAC) had good agreement with both the overall subjective and objective score, with the kappa of 0.778 and 0.547, respectively. In the objective indices, BCE (breast compliance evaluation), LBC (lower breast contour), and UNR (unilateral nipple retraction) correlated significantly with the subjective subdomains: location of the NAC, breast size, and shape (p < 0.05 for all indices). Conclusions: Good agreement exists for overall cosmetic outcomes measured by subjective and objective methods. Location of the NAC, breast size and shape are the most important parameters determining cosmetic outcomes irrespective of the method of assessment.

17.
Radiother Oncol ; 129(1): 173-179, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30318170

RESUMO

PURPOSE: To investigate dosimetric impact of inter-observer variation in clinical target volume(CTV) delineation for patients undergoing interstitial partial breast brachytherapy. METHODS: Five radiation oncologists delineated CTV in twenty patients who underwent multi-catheter partial breast brachytherapy. Five treatment plans for each patient were graphically optimized for CTV of all observers and evaluated using coverage index(CI), external volume index(EI), overdose volume index(OI) and conformal index(COIN). In addition, volume enclosed by prescription isodose(V100), its spatial concordance(CIcommon), mean coverage of all CTVs with common volume of prescription dose(V100_common) and mean CTV coverage for all pairs of observer with common prescription volume of respective pairs(V100_pair) were also computed. RESULTS: The mean ±â€¯standard deviation(SD) of CI and COIN ranged from 0.756 ±â€¯0.076 to 0.840 ±â€¯0.070 and 0.591 ±â€¯0.090 to 0.673 ±â€¯0.06 respectively. When a plan made for CTV of individual observer was evaluated on CTV of all observers, the maximum variations(ρ < 0.05) in the mean CI,COIN,OI and EI were 10.6%,11.4%,10.6% and 72.7% respectively. The observed mean ±â€¯SD of V100, CIcommon of V100, CTV coverage with V100_common and V100_pair was 160.7 ±â€¯52.1, 0.70 ±â€¯0.09, 73.1 ±â€¯8.1% and 77.9 ±â€¯7.3% respectively. CONCLUSION: Inter-observer variation in delineation of CTV showed significant dosimetric impact with mean CTV coverage of 73.1% and 77.9% by common and paired prescription dose volume respectively among all observers.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Braquiterapia/instrumentação , Cateterismo , Cateteres , Feminino , Humanos , Variações Dependentes do Observador , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X
18.
Indian J Cancer ; 55(1): 16-22, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147088

RESUMO

Background: Survival studies may serve as benchmarks to develop cancer-related policies and estimate baseline survival rates in a given patient population. Materials and Methods: We carried out a retrospective audit of cases managed in 2009 and now report the disease-free survival (DFS) in early breast cancer (EBC) and locally advanced breast cancer (LABC) in patients registered at a tertiary cancer center in India. Results: The study included 2192 patients with breast cancer with ages ranging from 18 years to 94 years with a median of 50 years. Of these, 888 (40.5%) were EBCs Stage I and II, 833 (38%) were LABCs (Stage III), and 471 (21.5%) were de novo metastatic or relapsed cancers at presentation. The 5-year DFS in the women with EBC was 85.5% and in LABC, it was 67.7%, P < 0.001. The factors adversely affecting DFS in EBC were node metastasis (P < 0.001), higher metastatic nodes (P < 0.001), hormone receptor negativity (P = 0.001), and human epidermal growth factor receptor 2 (Her2neu) positivity (P = 0.033). In the multivariate Cox regression analysis in EBC, node-positive status (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.51-3.45, P < 0.001) and hormone receptor negative tumors (HR 1.96, 95% CI 1.30-2.94, P = 0.001) significantly affected DFS in EBC. The factors adversely affecting DFS in LABC in the univariate analysis were node metastasis (P < 0.001), increasing numbers of nodes (P < 0.001), presence of lymphovascular emboli (LVE) (P < 0.01), mastectomy (P < 0.001), and Her2neu positivity (P = 0.03). In the multivariate Cox regression analysis, node positivity (HR 2.96, 95% CI 2.04-4.29, P < 0.0001), presence of LVE (HR 1.47, 95% CI 1.06-2.04, P = 0.023), and mastectomy (HR 1.49, 95% CI 1.06-2.10, P = 0.023) adversely impacted DFS in LABC. Conclusions: The survival rates in this study are equal to the documented global rates; nodal disease burden emerged as the most important prognostic factor. In addition, in EBCs, a lack of hormone receptor expression and in LABC, Her2neu overexpression appear to worsen the outcome.


Assuntos
Neoplasias da Mama/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
19.
J Contemp Brachytherapy ; 10(1): 47-57, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29619056

RESUMO

Purpose: The purpose of this study was to report clinical outcomes in patients treated with accelerated partial breast irradiation (APBI), stratified as per molecular subtype and American Society for Therapeutic Radiology and Oncology/Groupe Européen de Curiethérapie and European Society for Radiotherapy & Oncology (ASTRO/GEC-ESTRO) patient selection criteria in order to determine whether molecular subtype should be recommended as one of the selection criteria for APBI. Material and methods: 157 early-stage breast cancers patients, treated with APBI using multi-catheter interstitial brachytherapy with ≥ 6 months follow-up were included. Molecular subtype was assigned based on estrogen/progesterone receptor (ER/PR), Her2neu and tumor grade. Patients were stratified into ASTRO and GEC-ESTRO risk groups, as per updated ASTRO consensus statement (CS) and GEC-ESTRO recommendation, respectively. The Kaplan-Meier method was used to calculate the time to event data of clinical outcomes. Results: With a median follow-up of 35 months, local control (LC) and locoregional control (LRC) were not significantly different among the different molecular subtypes (p = 0.19, p = 0.41, respectively). None of the APBI guidelines predicted risk of local or locoregional recurrence. Re-analyzing the data by replacing ER status with molecular subtype in the ASTRO-CS did not show any significant difference in LC/LRC across the various categories. Her2neu subtype was associated with significantly lower disease-free survival, cause specific survival, and overall survival than the luminal subtypes. Conclusions: None of the mentioned APBI guidelines predicted local or locoregional recurrence risk in our study population. Additional follow-up will be needed to recommend inclusion of molecular subtype (or at least HER2 receptor status) in the patient selection criteria for APBI.

20.
Clin Breast Cancer ; 18(4): e727-e737, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29254601

RESUMO

BACKGROUND: Bilateral breast cancer (BBC) is an uncommon presentation. The characteristics and outcomes of synchronous and metachronous BBC were compared within an Indian cohort. PATIENTS AND METHODS: This was a retrospective audit of 193 BBC patients treated at a tertiary hospital in India over a period of 10 years from January 2004 to December 2014. The demographic, tumor and treatment characteristics were compared between synchronous (n = 131 patients) and metachronous tumors (n = 62 patients) using descriptive analysis. The survival outcomes were assessed using Kaplan-Meier survival curves and compared using the log rank test. Univariate and multivariate analysis was done using a Cox proportional hazards model to assess the effect of the prognostic factors on survival. RESULTS: The mean age of presentation in synchronous BBC (SBBC) and metachronous BBC (MBBC) was 55 years (SD, 12.5) and 51 years (SD, 9.5), respectively. The median time to contralateral presentation in MBBC was 3.8 years. Mean tumor size was larger in SBBC (P = .01). Breast Cancer gene mutation was positive in 13 of 38 evaluated patients (of whom 12 had MBBC). The concordance rates for the estrogen receptor (ER) and progesterone receptor negativity and triple-negative receptor status were higher in MBBC compared with SBBC (P < .001). Grade III tumor was more frequently seen in MBBC (P = .03). The median follow-up of the entire cohort was 42 months (range, 30-60 months): 45 months for SBBC and 35 months for MBBC. The 3-year rates of overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) for SBBC and MBBC was 88% and 90%, 74% and 64% and 90% and 84%, respectively. There was no difference in overall OS, DFS, and LRC between SBBC and MBBC. CONCLUSION: BBC is an uncommon presentation. Synchronous presentation was more common. Metachronous tumors differ from synchronous with higher Grade of presentation and less expression of ER. There was no difference in outcome between patients with synchronous and metachronous tumors.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Adulto , Idoso , Proteína BRCA1/genética , Neoplasias da Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/mortalidade , Segunda Neoplasia Primária/mortalidade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
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