Deep inspiration breath hold: dosimetric benefits to decrease cardiac dose during postoperative radiation therapy for breast cancer patients.

Background: Postoperative radiation therapy (RT) is the standard treatment for almost all patients diagnosed with breast cancer. Even with modern RT techniques, parts of the heart may still receive higher doses than those recommended by clinically validated dose limit restrictions, especially when the left breast is irradiated. Deep inspiration breath hold (DIBH) may reduce irradiated cardiac volume compared to free breathing (FB) treatment. This study aimed to evaluate the dosimetric impact on the heart and left anterior descending coronary artery (LAD) in FB and DIBH RT planning in patients with left breast cancer. Materials and methods: A retrospective cohort study of women diagnosed with left-sided breast cancer submitted to breast surgery followed by postoperative RT from 2015 to 2019. All patients were planned with FB and DIBH and hypofractionated dose prescription (40.05 Gy in 15 fractions). Results: 68 patients were included in the study. For the coverage of the planned target volume evaluation [planning target volume (PTV) eval] there was no significant difference between the DIBH versus FB planning. For the heart and LAD parameters, all constraints evaluated favored DIBH planning, with statistical significance. Regarding the heart, median V16.8 Gy was 2.56% in FB vs. 0% in DIBH (p < 0.001); median V8.8 Gy was 3.47% in FB vs. 0% in DIBH (p < 0.001) and the median of mean heart dose was 1.97 Gy in FB vs. 0.92 Gy in DIBH (p < 0.001). For the LAD constraints D2% < 42 Gy, the median dose was 34.87 Gy in FB versus 5.8 Gy in DIBH (p < 0.001); V16.8 Gy < 10%, the median was 15.87% in FB versus 0% in DIBH (p < 0.001) and the median of mean LAD dose was 8.13Gy in FB versus 2.92Gy in DIBH (p < 0.001). Conclusions: The DIBH technique has consistently demonstrated a significant dose reduction in the heart and LAD in all evaluated constraints, while keeping the same dose coverage in the PTV eval.

Can we predict who will benefit from the deep inspiration breath hold (DIBH) technique for breast cancer irradiation?

Background: The objective was to explore the clinical use of an "in-house" prototype developed to monitor respiratory motion to implement the deep inspiration breath hold technique (DIBH), compare dosimetric differences, and assess whether simple anatomic metrics measured on free breathing (FB) computed tomography scan (CT) can help in selecting patients that would benefit the most from the technique. Materials and methods: A prospective study was conducted on patients with left breast cancer with an indication of adjuvant radiotherapy for breast only. Treatment simulation consisted of four series of CTs: the first during FB and three in DIBH to assess the reproducibility and stability of apnea. Contouring was based on the RTOG atlas, and planning was done in both FB and DIBH. Dosimetric and geometric parameters were assessed and compared between FB and DIBH. Results: From June 2020 to December 2021, 30 patients with left breast cancer were recruited. Overall, the DIBH technique presented a mean dose reduction of 24% in the heart and 30% in the left anterior descendent coronary artery (LAD) (p < 0.05). The only geometric parameter correlated to a 30% dose reduction in the mean heart dose and LAD doses was the anterolateral distance from the heart to the chest wall of at least 1.5 cm measured on FB (p < 0.0001). Conclusion: The prototype enabled the use of the DIBH technique with dose reductions in the heart and LAD. The benefit of the DIBH technique can be predicted on FB CT by measuring the distance between the heart and chest wall at the treatment isocenter.

Applying PET-CT for predicting the efficacy of SBRT to inoperable early-stage lung adenocarcinoma: A Brazilian case-series.

Background: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage inoperable primary lung cancer. Here we report a thorough description of the prognostic value of pre-SBRT SUVmax for predicting the efficacy of SBRT in early-stage lung adenocarcinoma. Methods: This is a retrospective study of consecutive cases of early-stage inoperable lung adenocarcinoma, staged with PET-CT, treated with SBRT between 2007 and 17. Kaplan-Meier (KM) curves were used to assess overall survival and compare time to event between those with PET-CT SUVmax values ≤ 5.0 and those > 5. Fisher's Exact tests and the Mann-Whitney U were used to compare the patient and clinical data of those with SUVmax≤5.0 and >5.0, and those with and without any failure. Findings: Amongst 50 lung carcinoma lesions, from 47 patients (34 (68%)-T1a or 5 (p = 0.112). In addition, 5 experienced a regional failure and 4 a distant failure. Higher PET-CT SUVmax values before SBRT were associated with an increased risk of any failure (36% versus 0%, p = 0.0040 on Fisher's Exact test) and faster time to event (p = 0.010, log rank test). Both acute and late toxicities profile were acceptable. Interpretation: Patients with early-stage inoperable lung adenocarcinoma present good clinical outcomes when treated with SBRT. We raised the hypothesis that the value of PET-CT SUVmax before SBRT may be an important predictive factor in disease control. Funding: None.

Complications after breast reconstruction with alloplastic material in breast cancer patients submitted or not to post mastectomy radiotherapy.

BACKGROUND AND PURPOSE: Breast reconstruction following mastectomy is a relevant element of breast cancer treatment. The purpose of this study was to evaluate the influence of radiotherapy (RT) on local complications in patients with breast cancer that had undergone breast reconstruction with alloplastic material. MATERIALS AND METHODS: Retrospective study of breast cancer patients submitted to mastectomy and breast reconstruction from 2009 to 2013. Clinical and treatment variables were correlated with early and late complications. RESULTS: 251 patients were included; mean age was 49.7 (25 to 78) years. Reconstruction was immediate in 94% of the patients, with 88% performed with a temporary tissue expander. Postoperative radiotherapy (RT) was delivered to 167 patients (66.5%). Early complications were present in 26.3% of the patients. Irradiated patients presented 5.4% incidence of late complications versus 2.4% for non-irradiated patients (p = 0.327). Diabetes (OR = 3.41 95% CI: 1.23-9.45, p = 0.018) and high body mass index (BMI) (OR = 2.65; 95% CI: 1.60-4.37, p < 0.0001) were the main risk factors. The overall incidence of late complications was 4.4%, with predominance of severe capsular contracture (8/11). Arterial hypertension (OR = 4.78; 95% CI: 1.97-11.63, p = 0.001), BMI (OR = 0.170; 95% CI: 0.048-0.607, p = 0.006) and implant placement (OR = 3.55; 95% CI: 1.26-9.99, p = 0.016) were related to late complications. CONCLUSIONS: The overall rate of complications was low in this population. Radiotherapy delivery translated into a higher but not statistically significant risk of late complications when compared with the non-irradiated patients. Already well-known clinical risk factors for complications after breast reconstruction were identified.

Vaginal cuff brachytherapy in the adjuvant setting for patients with high-risk early-stage cervical cancer.

PURPOSE: To evaluate local control and survival of high-risk patients with early-stage cervical cancer submitted or not to vaginal cuff brachytherapy in the postoperative setting. METHODS AND MATERIALS: In this retrospective cohort of patients treated from 2010 to 2017, patients were eligible if they had confirmed histological diagnosis of cervical cancer treated with surgery and adjuvant radiotherapy with or without chemotherapy. Vaginal cuff brachytherapy (VCB) was indicated according to the radiation oncologist discretion. RESULTS: Seventy-nine patients were selected, with a median age at diagnosis of 47.5 years (26-77). Brachytherapy was delivered to 59 patients (74.7%). There were no significant differences between the VCB and the no-VCB groups. A total of 13 (16.5%) patients presented one or more events, 5 (25%) and 8 (13.5%) events in the no-VCB and VCB group, respectively. Most recurrences were pelvic and/or vaginal: 7/20 (35%) in the no-VCB group and 9/59 (10.2%) in the VCB group. There were eight systemic relapses with eight deaths. With a median followup of 45 months, mean overall survival and disease-free survival were, respectively, 85.1 and 83.8 months. No variables were correlated with overall survival. The only factor positively correlated to disease-free survival was VCB, with a mean of 86.9 and 68.4 months for patients who did and did not receive brachytherapy, respectively (p = 0.043). Vaginal recurrence was lower in the brachytherapy group, but with no statistical significance (p = 0.065). CONCLUSION: VCB was associated with a reduced recurrence rate in the postoperative setting of high-risk patients with early-stage cervical cancer.

Stereotactic Body Radiation Therapy for Biopsy-Proven Primary Non-Small-Cell Lung Cancer: Experience of Patients With Inoperable Cancer at a Single Brazilian Institution.

Purpose Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for patients with non-small-cell lung cancer (NSCLC). We report the clinical outcomes and toxicity for patients with inoperable primary NSCLC treated with SBRT. Methods Between 2007 and 2015, 102 consecutive lung lesions were treated with SBRT at our center, of which 59 primary NSCLC lesions (from 54 patients with inoperable disease) were retrospectively reviewed (43 lesions were excluded because of metastases or because there was no biopsy specimen). We report infield local control (LC) per SBRT target, regional or distant failure-free survival, and overall survival (OS) per patient, using Kaplan-Meier estimates. Serious toxicity was retrospectively scored using Common Terminology Criteria for Adverse Events, version 4. Results Most of the 54 patients were men (n = 41; 76%), median age was 75 years; stage IA (n = 36; 66%) and adenocarcinoma (n = 43; 80%) were the most common stage and histologic diagnosis, respectively. Five patients had two lung lesions. A median of three fractions (range, 3 to 5 fractions) and a total median dose of 54 Gy (range, 45 to 60 Gy) per lesion were prescribed. The median follow-up was 17.8 months (range, 4 to 56.4 months). The 2-year rates of LC, regional or distant failure-free survival, and OS were 89.1% (95% CI, 72.2% to 96%), 79% (95% CI, 59.8% to 89.8%), and 80% (95% CI, 64% to 89.8%), respectively. Grade 3 to 4 toxicities were observed in two patients (3%): grade 3 pneumonitis (n = 1) and grade 4 skin toxicity (n = 1). Conclusion SBRT results in high rates of 2-year LC, regional or distant failure-free survival, and OS with low rates of severe toxicity in patients with inoperable primary NSCLC disease.

Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials.

PURPOSE: We aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. MATERIALS AND METHODS: We searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). RESULTS: 1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. CONCLUSIONS: nPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals.

Intraoperative full-dose of partial breast irradiation with electrons delivered by standard linear accelerators for early breast cancer.

Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma (T ≤ 3.0 cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40-85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC.

Outcomes of high-dose intensity-modulated radiotherapy alone with 1 cm planning target volume posterior margin for localized prostate cancer.

BACKGROUND: Clinically localized prostate cancer may be treated by different approaches of radiation therapy. The aim of this study was to report the results of disease control and toxicity in patients with clinically localized prostate cancer treated with high dose IMRT alone with 1 cm PTV posterior margin. METHODS: From September 2001 to April 2008, 140 patients with localized prostate cancer were treated with definitive IMRT (dose ≥ 74 Gy) without hormone therapy. Outcomes were measured from the conclusion of radiotherapy. Biochemical failure was defined as PSA nadir + 2.0 ng/dL. Toxicities were assessed using the NCI-CTCAE-version 3.0. Median follow-up was 58 months. RESULTS: Biochemical failure occurred in 13.6% of patients. Actuarial 5-year biochemical control rates were 91.7%, 82.5% and 85.9% for low-, intermediate-, and high-risk patients, respectively. Stage T2 patients presented a risk of biochemical failure almost three times higher than stage T1 (RR = 2.91; 95% CI: 1.04; 8.17). Distant metastases occurred in 3 (2%) patients. Five-year metastasis-free and overall survivals were 96% and 97.5%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity rates were, respectively, 1.6% and 3%. CONCLUSION: High-dose IMRT alone with 1 cm posterior PTV margin was effective and safe for patients with localized prostate cancer.

Immunohistochemical analysis of p53, APE1, hMSH2 and ERCC1 proteins in actinic cheilitis and lip squamous cell carcinoma.

AIMS: This study has compared the tissue expression of the p53 tumour suppressor protein and DNA repair proteins APE1, hMSH2 and ERCC1 in normal, dysplastic and malignant lip epithelium. METHODS AND RESULTS: Morphological analysis and immunohistochemistry were performed on archived specimens of normal lip mucosa (n=15), actinic cheilitis (AC) (n=30), and lip squamous cell carcinoma (LSCC) (n=27). AC samples were classified morphologically according to the severity of epithelial dysplasia and risk of malignant transformation. LSCC samples were morphologically staged according to WHO and invasive front grading (IFG) criteria. Differences between groups and morphological stages were determined by bivariate statistical analysis. Progressive increases in the percentage of epithelial cells expressing p53 and APE1 were associated with increases in morphological malignancy from normal lip mucosa to LSCC. There was also a significant reduction in epithelial cells expressing hMSH2 and ERCC1 proteins in the AC and LSCC groups. A higher percentage of malignant cells expressing APE1 was found in samples with an aggressive morphological IFG grade. CONCLUSIONS: Our data showed that epithelial cells from premalignant to malignant lip disease exhibited changes in the expression of p53, APE1, hMSH2 and ERCC1 proteins; these molecular change might contribute to lip carcinogenesis.

Experiência com um sistema de informações via Internet sobre radioterapia / Experience with an Internet information system about radiotherapy

Foi criado um canal independente de informações acerca do tratamento do câncer com radioterapia: o site "www.iradioterapia.com", que disponibiliza informações na Internet, tendo como base dados científicos e linhas de condutas diversas. Sempre de modo ético, profissionais da saúde, estudantes, pacientes e familiares, entre outros, podem obter informações teóricas a respeito de condutas, opções terapêuticas e atualizações em relação aos tratamentos disponíveis em nível mundial, além de tira-dúvidas on-line. Podem também participar de grupos de debates entre os próprios interessados. Na rede desde agosto/2000, já foram registrados 4000 acessos, com dezenas de dúvidas de pacientes respondidas e fóruns realizados. As principais questões levantadas são a respeito de condutas médicas, cuidados com o paciente e prognóstico da doença. Nota-se ausência de informações dirigidas à pacientes e familiares acerca do tratamento radioterápico. O acesso democrático e livre de informações ligadas à saúde e medicina possibilita a melhoria das técnicas de tratamento, da relação médico-paciente e tranqüilização do paciente durante o tratamento. O sistema de acesso a informações via Internet permitiu melhor participação dos pacientes e seus familiares no seu tratamento, propiciando maior conforto e tranqüilidade. Com informação acessível, pacientes colaboram nas consultas com seus médicos e buscam melhores opções técnicas.

Tratamento do câncer do endométrio com braquiterapia de alta taxa de dose / Treatment of endometrium neoplasm with high dose rate brachytherapy

Cento e quatro pacientes com histologia comprovada de carcinoma do endométrio foram tratadas desde a instalaçao da BATD no Departamento, em 1991. A idade mediana foi de 65,5 anos e o seguimento mediano de 38 meses. Noventa e cinco eram pós-menopausadas, sete peri-menopausadas e duas estavam na pré-menopausa. Dezesseis pacientes eram do estádio clínico (pós-cirúrgico) EC IA, sendo cinco com grau de diferenciaçao Gl, oito G2 e três G3. Trinta e quatro pacientes eram do EC IB, dez com grau de diferenciaçao Gl, 18 G2 e seis G3. Vinte e cinco eram do EC IC, sendo nove Gl, nove G2 e sete G3. Seis eram do EC IIA, duas Gl, três G2 e uma G3. Oito eram do EC IIB, uma Gl, três G2 e quatro G3. Nove eram do EC IIIA, duas Gl, cinco G2 e duas G3. Três eram do EC IIIB, sendo duas Gl e uma G2. Uma era EC IIIC G3 e duas eram IVA G3. Dependendo da extensao da doença, a cirurgia consistiu de pan-histerectomia (Histerectomia total mais salpingooforectomia bilateral), pan-histerectomia mais omentectomia ou Wertheim-Meigs. Todas as pacientes dos estádios clínicos IA e IB apresentam-se sem evidência de doença (SED). As do EC IC 24 estao SED e uma apresentou metástases (MAD). As do EC IIA, cinco estao SED e uma MAD. As do EC IIB, seis estao SED, uma com progressao de doença local (PDL) e uma foi a óbito (OPD). As do EC IIIA, sete estao SED, uma MAD e uma apresentou progressao de doença. As do EC IIIB l está SED e duas apresentam progressao de doença. A paciente IIIC está SED, dois meses após o tratamento, e as IVA se apresentam SED, três e quatro meses após o término do tratamento. Oito pacientes apresentaram complicaçoes leves de tratamento Os resultados sao semelhantes aos dos tratamentos com braquiterapia de baixa taxa de dose, tanto em sobrevida como em complicaçao, com a vantagem de ser realizado em regime ambulatorial , sem os inconvenientes de uma internaçao hospitalar.