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1.
Cochrane Database Syst Rev ; 8: CD007077, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459500

RESUMO

BACKGROUND: Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast-conserving therapy for early-stage breast cancer. SEARCH METHODS: On 27 August 2020, we searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and three trial databases. We searched for grey literature: OpenGrey (September 2020), reference lists of articles, conference proceedings and published abstracts, and applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors (BH and ML) performed data extraction, used Cochrane's risk of bias tool and resolved any disagreements through discussion, and assessed the certainty of the evidence for main outcomes using GRADE. Main outcomes were local recurrence-free survival, cosmesis, overall survival, toxicity (subcutaneous fibrosis), cause-specific survival, distant metastasis-free survival and subsequent mastectomy. We entered data into Review Manager 5 for analysis. MAIN RESULTS: We included nine RCTs that enrolled 15,187 women who had invasive breast cancer or ductal carcinoma in-situ (6.3%) with T1-2N0-1M0 Grade I or II unifocal tumours (less than 2 cm or 3 cm or less) treated with breast-conserving therapy with negative margins. This is the second update of the review and includes two new studies and 4432 more participants. Local recurrence-free survival is probably slightly reduced (by 3/1000, 95% CI 6 fewer to 0 fewer) with the use of PBI/APBI compared to WBRT (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 8 studies, 13,168 participants; moderate-certainty evidence). Cosmesis (physician/nurse-reported) is probably worse (by 63/1000, 95% CI 35 more to 92 more) with the use of PBI/APBI (odds ratio (OR) 1.57, 95% CI 1.31 to 1.87; 6 studies, 3652 participants; moderate-certainty evidence). Overall survival is similar (0/1000 fewer, 95% CI 6 fewer to 6 more) with PBI/APBI and WBRT (HR 0.99, 95% CI 0.88 to 1.12; 8 studies, 13,175 participants; high-certainty evidence). Late radiation toxicity (subcutaneous fibrosis) is probably increased (by 14/1000 more, 95% CI 102 more to 188 more) with PBI/APBI (OR 5.07, 95% CI 3.81 to 6.74; 2 studies, 3011 participants; moderate-certainty evidence). The use of PBI/APBI probably makes little difference (1/1000 less, 95% CI 6 fewer to 3 more) to cause-specific survival (HR 1.06, 95% CI 0.83 to 1.36; 7 studies, 9865 participants; moderate-certainty evidence). We found the use of PBI/APBI compared with WBRT probably makes little or no difference (1/1000 fewer (95% CI 4 fewer to 6 more)) to distant metastasis-free survival (HR 0.95, 95% CI 0.80 to 1.13; 7 studies, 11,033 participants; moderate-certainty evidence). We found the use of PBI/APBI in comparison with WBRT makes little or no difference (2/1000 fewer, 95% CI 20 fewer to 20 more) to mastectomy rates (OR 0.98, 95% CI 0.78 to 1.23; 3 studies, 3740 participants, high-certainty evidence). AUTHORS' CONCLUSIONS: It appeared that local recurrence-free survival is probably worse with PBI/APBI; however, the difference was small and nearly all women remain free of local recurrence. Overall survival is similar with PBI/APBI and WBRT, and we found little to no difference in other oncological outcomes. Some late effects (subcutaneous fibrosis) may be worse with PBI/APBI and its use is probably associated with worse cosmetic outcomes. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver PBI/APBI. We await completion of ongoing trials.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Hipofracionamento da Dose de Radiação
2.
Cochrane Database Syst Rev ; 7: CD007077, 2016 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-27425375

RESUMO

BACKGROUND: Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. SELECTION CRITERIA: Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. MAIN RESULTS: We included seven RCTs and studied 7586 women of the 8955 enrolled.Local recurrence-free survival appeared worse for women receiving PBI/APBI compared to WBRT (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.11 to 2.35; six studies, 6820 participants, low-quality evidence). Cosmesis (physician-reported) appeared worse with PBI/APBI (odds ratio (OR) 1.51, 95% CI 1.17 to 1.95, five studies, 1720 participants, low-quality evidence). Overall survival did not differ with PBI/APBI (HR 0.90, 95% CI 0.74 to 1.09, five studies, 6718 participants, high-quality evidence).Late radiation toxicity (subcutaneous fibrosis) appeared worse with PBI/APBI (OR 6.58, 95% CI 3.08 to 14.06, one study, 766 participants, moderate-quality evidence). Acute skin toxicity appeared reduced with PBI/APBI (OR 0.04, 95% CI 0.02 to 0.09, two studies, 608 participants). Telangiectasia (OR 26.56, 95% CI 3.59 to 196.51, 1 study, 766 participants) and radiological fat necrosis (OR 1.58, 95% CI 1.02 to 2.43, three studies, 1319 participants) appeared worse with PBI/APBI. Late skin toxicity (OR 0.21, 95% CI 0.01 to 4.39, two studies, 608 participants) and breast pain (OR 2.17, 95% CI 0.56 to 8.44, one study, 766 participants) appeared not to differ with PBI/APBI.'Elsewhere primaries' (new primaries in the ipsilateral breast) appeared more frequent with PBI/APBI (OR 3.97, 95% CI 1.51 to 10.41, three studies, 3009 participants).We found no clear evidence of a difference for the comparison of PBI/APBI with WBRT for the outcomes of: cause-specific survival (HR 1.08, 95% CI 0.73 to 1.58, five studies, 6718 participants, moderate-quality evidence), distant metastasis-free survival (HR 0.94, 95% CI 0.65 to 1.37, four studies, 3267 participants, moderate-quality evidence), relapse-free survival (HR 1.36, 95% CI 0.88 to 2.09, three studies, 3811 participants), loco-regional recurrence-free survival (HR 1.80, 95% CI 1.00 to 3.25, two studies, 3553 participants) or mastectomy rates (OR 1.20, 95% CI 0.77 to 1.87, three studies, 4817 participants, low-quality evidence). Compliance was met: more than 90% of the women in all studies received the RT they were assigned to receive. We found no data for the outcomes of costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: It appeared that local recurrence and 'elsewhere primaries' (new primaries in the ipsilateral breast) are increased with PBI/APBI (the difference was small), but we found no evidence of detriment to other oncological outcomes. It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.


Assuntos
Neoplasias da Mama/radioterapia , Tratamentos com Preservação do Órgão/métodos , Mama/efeitos da radiação , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/prevenção & controle , Hipofracionamento da Dose de Radiação , Radioterapia/efeitos adversos , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Cochrane Database Syst Rev ; 7: CD003860, 2016 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-27425588

RESUMO

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an update of a Cochrane Review first published in 2008 and updated in 2009. OBJECTIVES: To assess the effect of altered radiation fraction size for women with early breast cancer who have had breast conserving surgery. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Register (23 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Jan 1996 to May 2015), EMBASE (Jan 1980 to May 2015), the WHO International Clinical Trials Registry Platform (ICTRP) search portal (June 2010 to May 2015) and ClinicalTrials.gov (16 April 2015), reference lists of articles and relevant conference proceedings. No language or publication constraints were applied. SELECTION CRITERIA: Randomised controlled trials of altered fraction size versus conventional fractionation for radiation therapy in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: Two authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: We studied 8228 women in nine studies. Eight out of nine studies were at low or unclear risk of bias. Altered fraction size (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not have a clinically meaningful effect on: local recurrence-free survival (Hazard Ratio (HR) 0.94, 95% CI 0.77 to 1.15, 7095 women, four studies, high-quality evidence), cosmetic outcome (Risk ratio (RR) 0.90, 95% CI 0.81 to 1.01, 2103 women, four studies, high-quality evidence) or overall survival (HR 0.91, 95% CI 0.80 to 1.03, 5685 women, three studies, high-quality evidence). Acute radiation skin toxicity (RR 0.32, 95% CI 0.22 to 0.45, 357 women, two studies) was reduced with altered fraction size. Late radiation subcutaneous toxicity did not differ with altered fraction size (RR 0.93, 95% CI 0.83 to 1.05, 5130 women, four studies, high-quality evidence). Breast cancer-specific survival (HR 0.91, 95% CI 0.78 to 1.06, 5685 women, three studies, high quality evidence) and relapse-free survival (HR 0.93, 95% CI 0.82 to 1.05, 5685 women, three studies, moderate-quality evidence) did not differ with altered fraction size. We found no data for mastectomy rate. Altered fraction size was associated with less patient-reported (P < 0.001) and physician-reported (P = 0.009) fatigue at six months (287 women, one study). We found no difference in the issue of altered fractionation for patient-reported outcomes of: physical well-being (P = 0.46), functional well-being (P = 0.38), emotional well-being (P = 0.58), social well-being (P = 0.32), breast cancer concerns (P = 0.94; 287 women, one study). We found no data with respect to costs. AUTHORS' CONCLUSIONS: We found that using altered fraction size regimens (greater than 2 Gy per fraction) does not have a clinically meaningful effect on local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance, late toxicity or patient-reported quality-of-life measures for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins.


Assuntos
Neoplasias da Mama/radioterapia , Hipofracionamento da Dose de Radiação , Neoplasias da Mama/cirurgia , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Mastectomia Segmentar , Lesões por Radiação/complicações , Lesões por Radiação/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Aust Fam Physician ; 45(11): 805-809, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27806449

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death in Australia. Radiotherapy plays an important role in the curative and palliative settings. OBJECTIVE: This article reviews recent technological advances that have expanded the radiotherapy treatment options available, and presents standard and emerging approaches to NSCLC. DISCUSSION: General practitioners play an integral role in the care and education of patients during diagnosis, treatment andfollow-up of NSCLC. Stereotactic (ablative) body radiotherapy,intensity-modulated radiotherapy, intracranial radiosurgery and hippocampal-avoidance whole-brain radiotherapy are discussed in this article.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Pulmão/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Pulmão/cirurgia , Radiocirurgia/instrumentação , Radiocirurgia/métodos , Radioterapia/instrumentação , Radioterapia/métodos , Técnicas de Imagem de Sincronização Respiratória/instrumentação , Técnicas de Imagem de Sincronização Respiratória/métodos
5.
Aust Fam Physician ; 44(9): 663-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26488048

RESUMO

BACKGROUND: One in five Australian men are diagnosed with prostate cancer. External beam radiation therapy (EBRT) is an effective treatment for men suitable for definitive therapy. OBJECTIVE: This article outlines the processes involved in EBRT for prostate cancer, with particular emphasis on recent technological advances that have had a positive impact on patient outcomes. The patient's experience is explained and comparisons are made with surgery. DISCUSSION: Patients diagnosed with localised prostate cancer may have multiple treatment options. General practitioners have an important role in helping patients navigate their way through the information needed to make this decision. Radiotherapy technologies, including image guidance, intensity-modulated radiation therapy and stereotactic (ablative) radiation therapy are discussed in this article.


Assuntos
Medicina Geral , Neoplasias da Próstata/radioterapia , Tecnologia Radiológica , Humanos , Masculino , Hipofracionamento da Dose de Radiação , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de Risco , Resultado do Tratamento
6.
Cochrane Database Syst Rev ; (6): CD007077, 2014 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-24938937

RESUMO

BACKGROUND: Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. DATA COLLECTION AND ANALYSIS: Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials, graded the methodological quality using Cochrane's Risk of Bias tool and resolved any disagreements through discussion. MAIN RESULTS: We included four RCTs that had 2253 women. Two older trials examined RT techniques which do not reflect current practice and one trial had a short follow-up. We downgraded the quality of the evidence for our key outcomes due to risk of bias. Taken together with other GRADE recommendations, the quality of evidence for our outcomes was very low to low. For the comparison of partial breast irradiation/accelerated breast irradiation (PBI/APBI) with whole breast irradiation (WBRT), local recurrence-free survival appeared worse (Hazard Ratio (HR) 1.74, 95% confidence interval (CI) 1.23 to 2.45; three trials, 1140 participants, very low quality evidence). Cosmesis appeared improved with PBI/APBI in a single trial (OR 0.40, 95% CI 0.23 to 0.72; one trial, 241 participants, very low quality evidence), but late toxicity (telangiectasia OR 4.41, 95% CI 3.21 to 6.05; very low quality evidence, 708 participants) and subcutaneous fibrosis (OR 4.27, 95% CI 3.04 to 6.01; one trial, 710 participants, very low quality evidence) appeared increased in another trial. We found no clear evidence of a difference for the comparison of PBI/APBI versus WBRT for the outcomes of: overall survival (HR 0.99, 95% CI 0.83 to 1.18; three trials, 1140 participants, very low quality evidence), cause-specific survival (HR 0.95, 95% CI 0.74 to 1.22; two trials, 966 participants, low evidence quality), distant metastasis-free survival (HR 1.02, 95% CI 0.81 to 1.28; 1140 participants, low quality evidence), subsequent mastectomy rate (OR 0.20, 95% CI 0.01 to 4.21; 258 participants, low quality evidence) and relapse-free survival (HR 0.99, 95% CI 0.53 to 1.85; 258 participants, low quality evidence). We found no data for the outcomes of acute toxicity, new ipsilateral breast primaries, costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.


Assuntos
Neoplasias da Mama/radioterapia , Tratamentos com Preservação do Órgão/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/prevenção & controle , Radioterapia/efeitos adversos , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Med Phys ; 49(1): 12-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828062

RESUMO

Introduction: Segmentation and analysis of organs at risks (OARs) and tumor volumes are integral concepts in the development of radiotherapy treatment plans and prediction of patients' treatment outcomes. Aims: To develop a research tool, PAHPhysRAD, that can be used to semi- and fully automate segmentation of OARs. In addition, the proposed software seeks to extract 3214 radiomic features from tumor volumes and user-specified dose-volume parameters. Materials and Methods: Developed within MATLAB, PAHPhysRAD provides a comprehensive suite of segmentation tools, including manual, semi-automatic, and automatic options. For semi-autosegmentation, meta AI's Segment Anything Model was incorporated using the bounding box methods. Autosegmentation of OARs and tumor volume are implemented through a module that enables the addition of models in Open Neural Network Exchange format. To validate the radiomic feature extraction module in PAHPhysRAD, radiomic features extracted from gross tumor volume of 15 non-small cell lung carcinoma patients were compared against the features extracted from 3D Slicer™. The dose-volume parameters extraction module was validated using the dose volume data extracted from 28 tangential field-based breast treatment planning datasets. The volume receiving ≥20 Gy (V20) for ipsilateral lung and the mean doses received by the heart and ipsilateral lung, were compared against the parameters extracted from Eclipse. Results: The Wilcoxon signed-rank test revealed no significant difference between the majority of the radiomic features derived from PAHPhysRAD and 3D Slicer. The average mean lung and heart doses calculated in Eclipse were 5.51 ± 2.28 Gy and 1.64 ± 1.98 Gy, respectively. Similarly, the average mean lung and heart doses calculated in PAHPhysRAD were 5.45 ± 2.89 Gy and 1.67 ± 2.08 Gy, respectively. Conclusion: The MATLAB-based graphical user interface, PAHPhysRAD, offers a user-friendly platform for viewing and analyzing medical scans with options to extract radiomic features and dose-volume parameters. Its versatility, compatibility, and potential for further development make it an asset in medical image analysis.

8.
Cochrane Database Syst Rev ; (4): CD005212, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23633328

RESUMO

BACKGROUND: After surgery for localised breast cancer, radiotherapy (RT) improves both local control and breast cancer-specific survival. In patients at risk of harbouring micro-metastatic disease, adjuvant chemotherapy (CT) improves 15-year survival. However, the best sequence of administering these two types of adjuvant therapy for early-stage breast cancer is unclear. OBJECTIVES: To determine the effects of different sequencing of adjuvant CT and RT for women with early breast cancer. SEARCH METHODS: An updated search was carried out in the Cochrane Breast Cancer Group's Specialised Register (20 May 2011), MEDLINE (14 December 2011), EMBASE (20 May 2011) and World Health Organization (WHO) International Clinical Trials Registry Platform (20 May 2011). Details of the search strategy and methods of coding for the Specialised Register are described in the Group's module in The Cochrane Library. We extracted studies that had been coded as 'early', 'chemotherapy' and 'radiotherapy'. SELECTION CRITERIA: We included randomised controlled trials evaluating different sequencing of CT and RT. DATA COLLECTION AND ANALYSIS: We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included trials. We derived odds ratios (OR) and hazard ratios (HR) from the available numerical data. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments. MAIN RESULTS: Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for local recurrence-free survival, overall survival, relapse-free survival and metastasis-free survival based on 1166 randomised women in three trials. Concurrent chemoradiation increased anaemia (OR 1.54; 95% confidence interval (CI) 1.10 to 2.15), telangiectasia (OR 3.85; 95% CI 1.37 to 10.87) and pigmentation (OR 15.96; 95% CI 2.06 to 123.68). Treated women did not report worse cosmesis with concurrent chemoradiation but physician-reported assessments did (OR 1.14; 95% CI 0.42 to 3.07). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), RT before CT was associated with an increased risk of neutropenic sepsis (OR 2.96; 95% CI 1.26 to 6.98) compared with CT before RT, but other measures of toxicity did not differ. AUTHORS' CONCLUSIONS: The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Quimioterapia Adjuvante/métodos , Radioterapia Adjuvante/métodos , Anemia/etiologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Transtornos da Pigmentação/etiologia , Radioterapia Adjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Telangiectasia/etiologia , Fatores de Tempo
9.
J Cancer Res Ther ; 19(2): 289-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313907

RESUMO

Aim: Current radiotherapy treatment techniques require a large amount of imaging data for treatment planning which demand significant clinician's time to segment target volume and organs at risk (OARs). In this study, we propose to use U-net-based architecture to segment OARs commonly encountered in lung cancer radiotherapy. Materials and Methods: Four U-Net OAR models were generated and trained on 20 lung cancer patients' computed tomography (CT) datasets, with each trained for 100 epochs. The model was tested for each OAR, including the right lung, left lung, heart, and spinal cord. Dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess the agreement between the predicted contour and ground truth. Results: The highest of the average DSC among the test patients for the left lung and the right lung was 0.96 ± 0.03 and 0.94 ± 0.06, respectively, and 0.88 ± 0.04 for heart, and 0.76 ± 0.07 for the spinal cord. The HD for these corresponding DSCs was 3.51 ± 0.85, 4.06 ± 1.12, 4.09 ± 0.85, and 2.76 ± 0.52 mm for left lung, right lung, heart, and spinal cord, respectively. Conclusion: The autosegmented regions predicted by right and left lung models matched well with the manual contours. However, in a few cases, the heart model struggled to outline the boundary precisely. The spinal cord model had the lowest DSC, which may be due to its small size. This is an ongoing study aimed to assist radiation oncologists in segmenting the OARs with minimal effort.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia Computadorizada por Raios X , Coração/diagnóstico por imagem , Pulmão/diagnóstico por imagem
10.
J Med Phys ; 48(2): 129-135, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576091

RESUMO

Purpose: Optimizers are widely utilized across various domains to enhance desired outcomes by either maximizing or minimizing objective functions. In the context of deep learning, they help to minimize the loss function and improve model's performance. This study aims to evaluate the accuracy of different optimizers employed for autosegmentation of non-small cell lung cancer (NSCLC) target volumes on thoracic computed tomography images utilized in oncology. Materials and Methods: The study utilized 112 patients, comprising 92 patients from "The Cancer Imaging Archive" (TCIA) and 20 of our local clinical patients, to evaluate the efficacy of various optimizers. The gross tumor volume was selected as the foreground mask for training and testing the models. Of the 92 TCIA patients, 57 were used for training and validation, and the remaining 35 for testing using nnU-Net. The performance of the final model was further evaluated on the 20 local clinical patient datasets. Six different optimizers, namely AdaDelta, AdaGrad, Adam, NAdam, RMSprop, and stochastic gradient descent (SGD), were investigated. To assess the agreement between the predicted volume and the ground truth, several metrics including Dice similarity coefficient (DSC), Jaccard index, sensitivity, precision, Hausdorff distance (HD), 95th percentile Hausdorff distance (HD95), and average symmetric surface distance (ASSD) were utilized. Results: The DSC values for AdaDelta, AdaGrad, Adam, NAdam, RMSprop, and SGD were 0.75, 0.84, 0.85, 0.84, 0.83, and 0.81, respectively, for the TCIA test data. However, when the model trained on TCIA datasets was applied to the clinical datasets, the DSC, HD, HD95, and ASSD metrics showed a statistically significant decrease in performance compared to the TCIA test datasets, indicating the presence of image and/or mask heterogeneity between the data sources. Conclusion: The choice of optimizer in deep learning is a critical factor that can significantly impact the performance of autosegmentation models. However, it is worth noting that the behavior of optimizers may vary when applied to new clinical datasets, which can lead to changes in models' performance. Therefore, selecting the appropriate optimizer for a specific task is essential to ensure optimal performance and generalizability of the model to different datasets.

11.
J Med Phys ; 48(1): 26-37, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342607

RESUMO

Aim: The aim of this study is to determine the variation in Hounsfield values with single and multi-slice methods using in-house software on fan-beam computed tomography (FCT), linear accelerator (linac) cone-beam computed tomography (CBCT), and Icon-CBCT datasets acquired using Gammex and advanced electron density (AED) phantoms. Materials and Methods: The AED phantom was scanned on a Toshiba computed tomography (CT) scanner, five linac-based CBCT X-ray volumetric imaging systems, and Leksell Gamma Knife Icon. The variation between single and multi-slice methods was assessed by comparing scans acquired using Gammex and AED phantoms. The variation in Hounsfield units (HUs) between seven different clinical protocols was assessed using the AED phantom. A CIRS Model 605 Radiosurgery Head Phantom (TED) phantom was scanned on all three imaging systems to assess the target dosimetric changes due to HU variation. An in-house software was developed in MATLAB to assess the HU statistics and the trend along the longitudinal axis. Results: The FCT dataset showed a minimal variation (central slice ± 3 HU) in HU values along the long axis. A similar trend was also observed between the studied clinical protocols acquired on FCT. Variation among multiple linac CBCTs was insignificant. In the case of the water insert, a maximum HU variation of -7.23 ± 68.67 was observed for Linac 1 towards the inferior end of the phantom. All five linacs appeared to have a similar trend in terms of HU variation from the proximal to the distal end of the phantom, with a few outliers for Linac 5. Among three imaging modalities, the maximum variation was observed in gamma knife CBCTs, whereas FCT showed no appreciable deviation from the central value. In terms of dosimetric comparison, the mean dose in CT and Linac CBCT scans differed by <0.5 Gy, whereas at least a 1 Gy difference was observed between CT and gamma knife CBCT. Conclusion: This study shows a minimal variation with FCT between single, volume-based, and multislice methods, and hence the current approach of determining the CT-electron density curve based on a single-slice method would be sufficient for producing a HU calibrations curve for treatment planning. However, CBCTs acquired on linac, and in particular, gamma knife systems, show noticeable variations along the long axis, which is likely to affect the dose calculations performed on CBCTs. It is highly recommended to assess the Hounsfield values on multiple slices before using the HU curve for dose calculations.

12.
J Med Radiat Sci ; 69(1): 98-107, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34432386

RESUMO

INTRODUCTION: Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. METHODS: Thirty early-stage whole breast patient datasets, 15 each left- and right-sided cases, were retrospectively selected. Five techniques were generated for each data set: three-dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) - (HYV), reduced arc VMAT - bowtie (BT), and BT flattening filter free (FFF) - (BTFFF). Plan goals and OARs were evaluated and compared between techniques. RESULTS: BT had the highest median conformity index (CI) values (0.82, IQR: 0.80-0.85 left and 0.83, IQR 0.80-0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90-1.55), and BTFFF recorded lower heart V2.5 Gy , V5 Gy ; median 3.96% (IQR: 2.90-6.80) and 0.90% (IQR: 0.50-1.50) respectively for left-sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p < 0.001) with BTFFF producing significantly lower doses across all measures: mean, V5 Gy , V10 Gy and V20 Gy . CONCLUSION: Overall BT and BTFFF techniques produced lower OAR doses and equivalent PTV coverage for WBRT. BT and BTFFF techniques increased contralateral lung and breast doses; however, these were within prescribed tolerances and comparable to results published in the literature.


Assuntos
Neoplasias da Mama , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Neoplasias da Mama/radioterapia , Feminino , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
13.
Cochrane Database Syst Rev ; (12): CD007234, 2011 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-22161411

RESUMO

BACKGROUND: Men who have a radical prostatectomy (RP) for prostate cancer that does not involve lymph nodes, but extends beyond the prostate capsule into the seminal vesicles or to surgical margins, are at increased risk of relapse. In men with these high risk factors, radiotherapy (RT) directed at the prostate bed after surgery may reduce this risk, and be curative. OBJECTIVES: To evaluate the effect of adjuvant RT following RP for prostate cancer in men with high risk features compared with RP. SEARCH METHODS: We searched the Cochrane Prostatic Diseases and Urological Cancers Specialised Register (23 February 2011), the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE (January 1966 to February 2011), PDQ® (Physician Data Query) trial registry databases for ongoing studies (2 November 2010), reference lists from selected studies and reviews, and handsearched relevant conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing RP followed by RT with RP alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion and bias and extracted data for analysis. Authors were contacted to clarify data and obtain missing information. MAIN RESULTS: We found three RCTs involving 1815 men. Adjuvant RT following prostatectomy did not affect overall survival at 5 years (RD (risk difference) 0.00; 95% CI -0.03 to 0.03), but improved survival at 10 years (RD -0.11; 95% CI -0.20 to -0.02). Adjuvant RT did not improve prostate cancer-specific mortality at 5 years (RD -0.01; 95% CI -0.03 to 0.00). Adjuvant RT did not reduce metastatic disease at 5 years (RD -0.00; 95% CI -0.04 to 0.03), but reduced it at 10 years (RD -0.11; 95% CI -0.20 to -0.01). It improved local control at 5 and 10 years (RD -0.10; 95% CI -0.13 to -0.06 and RD -0.14; 95% CI -0.21 to -0.07, respectively), and biochemical progression-free survival at 5 years and 10 years (RD -0.16; 95% CI -0.21 to -0.11 and RD -0.29; 95% CI -0.39 to -0.19, respectively). There were no data for clinical disease-free survival. Adjuvant RT increased acute and late gastrointestinal toxicity [do you have the rd for this?], urinary stricture (RD 0.05; 95% CI 0.01 to 0.09) and incontinence (RD 0.04; 95% CI 0.01 to 0.08). It did not increase erectile dysfunction or degrade quality of life (RD 0.01; 95% CI -0.06 to -0.26), but with limited data. AUTHORS' CONCLUSIONS: Adjuvant RT after RP improves overall survival and reduces the rate of distant metastases, but these effects are only evident with longer follow up. At 5 and 10 years it improves local control and reduces the risk of biochemical failure, although the latter is not a clinical endpoint. Moderate or severe acute and late toxicity is minimal. There is an increased risk of urinary stricture and incontinence, but no detriment to quality of life, based on limited data. Given that the majority of men who have undergone a RP have a longer life expectancy, radiotherapy should be considered for those with high-risk features following radical prostatectomy. The optimal timing is unclear.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Humanos , Masculino , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
14.
J Med Imaging Radiat Oncol ; 65(6): 755-759, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33973400

RESUMO

INTRODUCTION: This cross-sectional study compared treatment recommendations made by a respiratory multi-disciplinary team with the treatment received by those patients in practice. The aim was to evaluate the rate at which patients were treated in keeping with MDT recommendations. It was hypothesised that most patients would be treated in accordance with these recommendations. These data were then used to provide a practical basis to consider the potential legal liability of multi-disciplinary teams. METHODS: All patients discussed in the Princess Alexandra Hospital Lung MDT over a three-month period were included. The recommendations made by the MDT were compared with the treatment received. Where available, the reason for any change in management plan was recorded. RESULTS: 74/109 evaluable patients were treated in accordance with the MDT recommendation. A further 7 patients had commenced treatment prior to MDT discussion. The most common reasons for change in management were patient choice (n = 6) or deterioration in clinical condition prior to treatment (n = 6). CONCLUSION: As hypothesised, there was a high rate of treatment in accordance with recommendations made by the MDT. Changes in management are mostly related to patient preference or change in condition after MDT discussion. In practice, there are only limited opportunities for an MDT to be liable for patient outcomes. It is suggested however that careful documentation and representation of cases where appropriate could further mitigate this risk.


Assuntos
Neoplasias Pulmonares , Equipe de Assistência ao Paciente , Estudos Transversais , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Seleção de Pacientes
15.
Pract Radiat Oncol ; 11(4): 252-263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33271352

RESUMO

PURPOSE: We compared intrathoracic symptom response rate, quality of life (QOL) and toxicity in patients with non-small cell lung cancer (NSCLC) not suitable for radical chemo-radiation therapy, experiencing symptoms from intrathoracic disease, who were randomized to receive palliative radiation therapy (PRT36/12) or concurrent chemotherapy and PRT (C-PRT40/20). METHODS AND MATERIALS: We included patients with stage III or IV NSCLC, with a Eastern Cooperative Oncology Group Performance status 0 to 1, who were experiencing at least one of the following: dyspnea, cough, hemoptysis, or chest pain. The primary outcome was a change in intrathoracic response rate from baseline to 6 weeks post completion of therapy using (1) a composite measure, the Intrathoracic Symptom Burden Index(ISBI), and (2) individual symptom scores measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire - Lung Cancer 13 item (QLQ-LC 13) instruments. RESULTS: Seventy-six patients were recruited with 68 eligible for analysis. In addition, 42.6% and 57.4% had stage III and IV disease, respectively. The Intrathoracic Symptom Burden Index was significantly lower at 6 weeks posttreatment than at baseline (adjusted mean difference -8.77, standard error 2.67; 95% confidence interval, -13.97% to -3.58%; P < .01) for the entire cohort with no difference between trial arms (P = .34). Both treatments provided effective palliation of individual symptoms with no significant difference between trial arms. QOL during treatment was significantly better for patients receiving C-PRT(40/20). There was no difference between arms in overall QOL between baseline and 6 weeks posttreatment. There was no difference in toxicity between treatment arms during treatment nor between baseline and 6 weeks posttreatment. There was no difference in progression-free survival. A nonstatistically significant 3-month improvement in median survival favored C-PRT(40/20). CONCLUSION: PRT(36/12) and C-PRT(40/20) provide effective symptom palliation in patients with stage III NSCLC not suitable for radical chemo-radiation therapy and in patients with stage IV disease. Chemotherapy added to PRT(40/20) does not provide superior symptomatic relief in this patient cohort.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Cuidados Paliativos , Qualidade de Vida
16.
J Med Phys ; 46(2): 80-87, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566287

RESUMO

PURPOSE: Fiducial marker seeds are often used as a surrogate to identify and track the positioning of prostate volume in the treatment of prostate cancer. Tracking the movement of prostate seeds aids in minimizing the prescription dose spillage outside the target volume to reduce normal tissue complications. In this study, You Only Look Once (YOLO) v2™ (MathWorks™) convolutional neural network was employed to train ground truth datasets and develop a program in MATLAB that can visualize and detect the seeds on projection images obtained from kilovoltage (kV) X-ray volume imaging (XVI) panel (Elekta™). METHODS: As a proof of concept, a wax phantom containing three gold marker seeds was imaged, and kV XVI seed images were labeled and used as ground truth to train the model. The projection images were corrected for any panel shift using flex map data. Upon successful testing, labeled marker seeds and projection images of three patients were used to train a model to detect fiducial marker seeds. A software program was developed to display the projection images in real-time and predict the seeds using YOLO v2 and determine the centers of the marker seeds on each image. RESULTS: The fiducial marker seeds were successfully detected in 98% of images from all gantry angles; the variation in the position of the seed center was within ± 1 mm. The percentage difference between the ground truth and the detected seeds was within 3%. CONCLUSION: Our study shows that deep learning can be used to detect fiducial marker seeds in kV images in real time. This is an ongoing study, and work is underway to extend it to other sites for tracking moving structures with minimal effort.

17.
Breast Cancer Res Treat ; 124(1): 163-75, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20734132

RESUMO

To evaluate the efficacy and economic efficiency of a multimedia, multimodal physical activity program for women undergoing adjuvant therapy following surgery for breast cancer. We conducted a randomized trial with concurrent incremental cost-effectiveness analysis and blinded baseline, 3, 6 and 12-month follow-up assessments amongst women undergoing adjuvant therapy following surgery for breast cancer (n = 89). The intervention was a multimedia, multimodal exercise program comprising strength, balance and endurance training elements. The control was sham flexibility and relaxation program delivered using similar materials. The primary outcome was health-related quality of life (EQ-5D & VAS, EORTC C30, BR23). Economic outcomes included direct health care costs and productivity gains and losses. Participants in the intervention group demonstrated greater improvement in health-related quality of life between baseline and the 3-month assessment [mean (sd) EQ-5D VAS (0-100) baseline: 72.6 (15.6), 3 month: 80.6 (11.6)] when compared to control group participants [baseline: 77.5 (13.5), 3 month: 74.1 (20.6), P = 0.006] and also improved more in terms of physical function [mean (sd) EORTC C30 physical function scale intervention (0-100) baseline: 84.9 (14.8), 3 month: 86.9 (10.7), control baseline: 91.3 (9.6), 3 month: 86.7 (14.9), P = 0.02]. These improvements were not sustained beyond this point. Upper limb volumes were also lower amongst intervention group participants. However, there was low probability that the intervention would be both less costly and more effective than the control condition (range probability = 0.05-50.02% depending on approach). Provision of multimodal exercise programs will improve the short-term health of women undergoing adjuvant therapy for breast cancer but are of questionable economic efficiency.


Assuntos
Neoplasias da Mama/terapia , Terapia por Exercício/economia , Custos de Cuidados de Saúde , Qualidade de Vida , Adulto , Idoso , Neoplasias da Mama/economia , Neoplasias da Mama/psicologia , Quimioterapia Adjuvante , Análise Custo-Benefício , Terapia por Exercício/efeitos adversos , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Queensland , Radioterapia Adjuvante , Recuperação de Função Fisiológica , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
18.
Cochrane Database Syst Rev ; (11): CD003860, 2010 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-21069678

RESUMO

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an updated version of the original Cochrane Review published in Issue 3, 2008. OBJECTIVES: To determine the effect of altered radiation fraction size on outcomes for women with early breast cancer who have undergone breast conserving surgery. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE and the WHO ICTRP search portal to June 2009, reference lists of articles and relevant conference proceedings. We applied no language constraints. SELECTION CRITERIA: Randomised controlled trials of unconventional versus conventional fractionation in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: The authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: Four trials reported on 7095 women. The women were highly selected: tumours were node negative and 89.8% were smaller than 3 cm. Where the breast size was known, 87% had small or medium breasts. The studies were of low to medium quality. Unconventional fractionation (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not affect: (1) local recurrence risk ratio (RR) 0.97 (95% CI 0.76 to 1.22, P = 0.78), (2) breast appearance RR 1.17 (95% CI 0.98 to 1.39, P = 0.09), (3) survival at five years RR 0.89 (95% CI 0.77 to 1.04, P = 0.16). Acute skin toxicity was decreased with unconventional fractionation: RR 0.21 (95% CI 0.07 to 0.64, P = 0.007). AUTHORS' CONCLUSIONS: Two new studies have been published since the last version of the review, altering our conclusions. We have evidence from four low to medium quality randomised trials that using unconventional fractionation regimens (greater than 2 Gy per fraction) does not affect local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance or late toxicity for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins. Long-term follow up (> 5 years) is available for a small proportion of the patients randomised. Longer follow up is required for a more complete assessment of the effect of altered fractionation.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Mastectomia Segmentar , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
ERJ Open Res ; 6(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32166087

RESUMO

This study investigated the effects of previous radiation therapy on outcomes from nivolumab in advanced NSCLC, and found that previous radiation therapy resulted in significantly higher survival in patients treated with nivolumab for advanced NSCLC http://bit.ly/3btOFSL.

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