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Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer. Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions. Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.
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PURPOSE OF REVIEW: Stereotactic body radiation therapy (SBRT) is increasingly utilized in the management of localized kidney cancers, particularly for patients who are not surgical candidates. Herein, we provide a narrative review of SBRT in the management of localized kidney cancers. RECENT FINDINGS: Recent prospective studies and multi-institutional retrospective studies highlight the safety and efficacy of SBRT in the management of renal tumors, a disease previously thought to be radioresistant. Studies have shown that local control is greater than 90% with rare grade 3 or 4 toxicity and no grade 5 toxicity. SBRT can be utilized successfully in the treatment of large kidney tumors (> 5 cm). New techniques such as MRI-guided radiation therapy may further improve the therapeutic ratio. However, randomized clinical trials are necessary to confirm the optimal dosing schedule and compare outcomes with nephrectomy, which remains the standard of care in suitable patients. Advances in SBRT have made this modality a safe and effective treatment option in the management of localized kidney cancers.
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Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Resultado do TratamentoRESUMO
"Radiomics," as it refers to the extraction and analysis of a large number of advanced quantitative radiological features from medical images using high-throughput methods, is perfectly suited as an engine for effectively sifting through the multiple series of prostate images from before, during, and after radiotherapy (RT). Multiparametric (mp)MRI, planning CT, and cone beam CT (CBCT) routinely acquired throughout RT and the radiomics pipeline are developed for extraction of thousands of variables. Radiomics data are in a format that is appropriate for building descriptive and predictive models relating image features to diagnostic, prognostic, or predictive information. Prediction of Gleason score, the histopathologic cancer grade, has been the mainstay of the radiomic efforts in prostate cancer. While Gleason score (GS) is still the best predictor of treatment outcome, there are other novel applications of quantitative imaging that are tailored to RT. In this review, we summarize the radiomics efforts and discuss several promising concepts such as delta-radiomics and radiogenomics for utilizing image features for assessment of the aggressiveness of prostate cancer and its outcome. We also discuss opportunities for quantitative imaging with the advance of instrumentation in MRI-guided therapies.
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Adenocarcinoma/radioterapia , Biologia Computacional , Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias da Próstata/radioterapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Hipóxia Celular , Fracionamento da Dose de Radiação , Humanos , Genômica por Imageamento , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Planejamento da Radioterapia Assistida por Computador , Resultado do Tratamento , Fluxo de TrabalhoRESUMO
PURPOSE: Develop a deep-learning-based segmentation algorithm for prostate and its peripheral zone (PZ) that is reliable across multiple MRI vendors. METHODS: This is a retrospective study. The dataset consisted of 550 MRIs (Siemens-330, General Electric[GE]-220). A multistream 3D convolutional neural network is used for automatic segmentation of the prostate and its PZ using T2-weighted (T2-w) MRI. Prostate and PZ were manually contoured on axial T2w. The network uses axial, coronal, and sagittal T2w series as input. The preprocessing of the input data includes bias correction, resampling, and image normalization. A dataset from two MRI vendors (Siemens and GE) is used to test the proposed network. Six different models were trained, three for the prostate and three for the PZ. Of the three, two were trained on data from each vendor separately, and a third (Combined) on the aggregate of the datasets. The Dice coefficient (DSC) is used to compare the manual and predicted segmentation. RESULTS: For prostate segmentation, the Combined model obtained DSCs of 0.893⯱ 0.036 and 0.825⯱ 0.112 (mean⯱ standard deviation) on Siemens and GE, respectively. For PZ, the best DSCs were from the Combined model: 0.811⯱ 0.079 and 0.788⯱ 0.093. While the Siemens model underperformed on the GE dataset and vice versa, the Combined model achieved robust performance on both datasets. CONCLUSION: The proposed network has a performance comparable to the interexpert variability for segmenting the prostate and its PZ. Combining images from different MRI vendors on the training of the network is of paramount importance for building a universal model for prostate and PZ segmentation.
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Aprendizado Profundo , Imageamento por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Algoritmos , Conjuntos de Dados como Assunto , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/instrumentação , Masculino , Próstata/patologia , Processos EstocásticosRESUMO
BACKGROUND: Circulating exosomes from prostate cancer (PCa) patients undergoing radiotherapy are attractive candidate biomarkers for monitoring treatment response. Multiple workflows for isolation and content characterization of exosomes in biofluids have been attempted. We report a protocol to isolate and characterize exosomal miRNAs content and assess radiation-induced changes. METHODS: In this pilot study, we performed targeted exosomal miRNA profiling of 25 serum samples obtained from PCa patients with intermediate- and high-risk disease treated with curative radiotherapy (RT), and controls. Post-treatment blood samples were collected at least 28 days after radiation therapy as a paired follow-up sample. The complete workflow consisted of two phases: I) filtration and polyethylene glycol salt precipitation phase which enriched particles below 200 nm in size followed by characterization using electron microscopy, and II) flow cytometry. Finally, miRNA expression analysis between untreated and treated patient samples was performed using RNA extraction kit, and qRT-PCR. RESULTS: In our preliminary data, 1 ml of serum from PCa patients showed higher exosomal concentration (3.68E+10) compared to controls (6.07E+08). The overall expression of exosomes after RT was found to be higher compared to untreated samples; the median value changed from 3.68E+10 to 5.40E+10; p = 0.52. Using electron microscopy, we were able to visualize cup-shaped vesicles with morphology and size compatible with exosomes. The bead-based flow cytometry showed positivity for exosomal tetraspanins surface markers CD63 and CD9. All five miRNAs (hsa-let-7a-5p, hsa-miR-141-3p, hsa-miR-145-5p, hsa-miR-21-5p, hsa-miR-99b-5p) have been identified in exosomes. Despite overall changes in hsa-let-7a-5p expression after radiation, the difference was significant only in the high-risk group (p = 0.037). In addition, the radiation response to hsa-miR-21-5p was elevated in the high-risk group compared to the intermediate group (p = 0.036). CONCLUSIONS: Herewith, we demonstrated a protocol for isolation of serum exosomes and exosomal miRNA amplification. The recovery of exosomal miRNAs and their differential expression after radiation treatment suggests promising biomarker potential that requires further investigation in larger patient cohorts.
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Exossomos/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Exossomos/ultraestrutura , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Risco , Tetraspanina 30/metabolismoRESUMO
INTRODUCTION: Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy. MATERIAL AND METHODS: A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology. RESULTS: The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined. CONCLUSION: We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.
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Recidiva Local de Neoplasia/radioterapia , Complicações Pós-Operatórias/radioterapia , Padrões de Prática Médica , Prostatectomia , Neoplasias da Próstata/radioterapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Terapia de Salvação , SuíçaRESUMO
BACKGROUND: The optimal treatment strategy for stage I-II glottic squamous cell carcinoma (SCC) is not well-defined. This study analyzed treatment results and prognostic factors. PATIENTS AND METHODS: This is a single-institution retrospective analysis of 244 patients with T1-2 glottic SCC who underwent normofractionated radiotherapy (RT) and/or surgery between 1990 and 2013. The primary endpoint was relapse-free survival (RFS). RESULTS: Median age was 65 years (range: 36-92 years), the majority (82%) having stage I disease. Definitive RT was used in 82% (median dose: 68 Gy, 2 Gy per fraction). Median follow-up was 59 months. The 5year RFS rates were 83 and 75% (p = 0.05) for stage I and 62 and 50% (p = 0.47) for stage II in the RT and surgery groups, respectively. Multivariate analyses indicate T1 vs. T2 and RT vs. surgery as independent prognostic factors for RFS, with hazard ratios of 0.38 (95% confidence interval, CI: 0.21-0.72) and 0.53 (95% CI: 0.30-0.99), respectively (p < 0.05). The 5year overall and cause-specific survival rates in the whole cohort were 92 and 96%, respectively, with no significant differences between treatment groups. Anterior commissure involvement was neither a prognostic nor a predictive factor. The incidence of secondary malignancies was not significantly different between patients treated with and without RT (22 vs. 9% at 10 years, respectively, p = 0.18). CONCLUSION: Despite a possible selection bias, our series demonstrates improved RFS with RT over surgery in stage I glottic SCC.
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Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Glote/patologia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/terapia , Laringectomia/mortalidade , Radioterapia Conformacional/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Terapia Combinada/métodos , Terapia Combinada/mortalidade , Intervalo Livre de Doença , Glote/efeitos da radiação , Glote/cirurgia , Humanos , Neoplasias Laríngeas/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Suíça/epidemiologia , Resultado do TratamentoRESUMO
INTRODUCTION: External beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), is an established treatment option for nonmetastatic prostate cancer. Despite high-level evidence from several randomized trials, risk group stratification and treatment recommendations vary due to contradictory or inconclusive data, particularly with regard to EBRT dose prescription and ADT duration. Our aim was to investigate current patterns of practice in primary EBRT for prostate cancer in Switzerland. MATERIALS AND METHODS: Treatment recommendations on EBRT and ADT for localized and locally advanced prostate cancer were collected from 23 Swiss radiation oncology centers. Written recommendations were converted into center-specific decision trees, and analyzed for consensus and differences using a dedicated software tool. Additionally, specific radiotherapy planning and delivery techniques from the participating centers were assessed. RESULTS: The most commonly prescribed radiation dose was 78 Gy (range 70-80 Gy) across all risk groups. ADT was recommended for intermediate-risk patients for 6 months in over 80 % of the centers, and for high-risk patients for 2 or 3 years in over 90 % of centers. For recommendations on combined EBRT and ADT treatment, consensus levels did not exceed 39 % in any clinical scenario. Arc-based intensity-modulated radiotherapy (IMRT) is implemented for routine prostate cancer radiotherapy by 96 % of the centers. CONCLUSION: Among Swiss radiation oncology centers, considerable ranges of radiotherapy dose and ADT duration are routinely offered for localized and locally advanced prostate cancer. In the vast majority of cases, doses and durations are within the range of those described in current evidence-based guidelines.
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Consenso , Padrões de Prática Médica , Neoplasias da Próstata/radioterapia , Antagonistas de Androgênios/uso terapêutico , Terapia Combinada , Árvores de Decisões , Medicina Baseada em Evidências , Fidelidade a Diretrizes , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , SuíçaRESUMO
BACKGROUND: Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS: We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS: Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION: This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING: Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Microambiente Tumoral/genética , DNA de Neoplasias/genética , Seguimentos , Genômica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
Intratumoral hypoxia is prevalent in many solid tumors and is a marker of poor clinical prognosis in prostate cancer. The presence of hypoxia is associated with increased chromosomal instability, gene amplification, downregulation of DNA damage repair pathways, and altered sensitivity to agents that damage DNA. These genomic changes could also lead to oncogene activation or tumor suppressor gene inactivation during prostate cancer progression. We review here the concept of repair-deficient hypoxic tumor cells that can adapt to low oxygen levels and acquire an aggressive "unstable mutator" phenotype. We speculate that hypoxia-induced genomic instability may also be a consequence of aberrant mitotic function in hypoxic cells, which leads to increased chromosomal instability and aneuploidy. Because both hypoxia and aneuploidy are prognostic factors in prostate cancer, a greater understanding of these biological states in prostate cancer may lead to novel prognostic and predictive tests and drive new therapeutic strategies in the context of personalized cancer medicine.
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Instabilidade Genômica , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Hipóxia Celular/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA/fisiologia , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/terapiaRESUMO
Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.
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Androgen deprivation therapy (ADT) is commonly used in the treatment of prostate cancer and is associated with several side effects including psychiatric disorders. We present an unusual case of a 62-year-old man with high risk prostate cancer that developed de novo psychosis after starting luteinizing hormone-releasing hormone (LHRH) agonists and discuss possible mechanisms to explain such findings. This case report highlights the importance of continuing assessment and monitoring of potential emotional and behavioral symptoms in prostate cancer patients treated with ADT.
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Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Psicoses Induzidas por Substâncias/diagnóstico , Pamoato de Triptorrelina/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Psicoses Induzidas por Substâncias/psicologia , Resultado do Tratamento , Pamoato de Triptorrelina/uso terapêuticoRESUMO
PURPOSE: Extending salvage radiotherapy to treat the pelvic lymph nodes (PLNRT) improves oncologic outcomes in prostate cancer (PCa). However, a larger treatment volume increases the extent of bone marrow (BM) exposure, which is associated with hematologic toxicity (HT). Given the potential long-term impact of BM dose in PCa, clinical studies on BM sparing (BMS) are warranted. Herein, we dosimetrically compared photon and proton plans for BMS. MATERIALS AND METHODS: Treatment plans of 20 post-operative PCa patients treated with volumetric-modulated arc photon therapy (VMAT) PLNRT were retrospectively identified. Contours were added for the whole pelvis BM (WPBM) and BM sub-volumes: lumbar-sacral (LSBM), iliac (ILBM), and lower pelvis (LPBM). Three additional plans were created: VMAT_BMS, intensity-modulated proton therapy (IMPT), and IMPT_BMS. Normal tissue complication probabilities (NTCP) for grade >3 hematologic toxicity (HT3+) were calculated for the WPBM volumes. RESULTS: Compared to the original VMAT plan, mean doses to all BM sub-volumes were statistically significantly lower for VMAT_BMS, IMPT, and IMPT_BMS resulting in average NTCP percentages of 20.5 ± 5.9, 10.7 ± 4.2, 6.1 ± 2.0, and 2.5 ± 0.6, respectively. IMPT_BMS had significantly lower low dose metrics (V300cGy-V2000cGy) for WPBM and sub-volumes except for LPBM V2000cGy compared to VMAT_BMS and ILBM V20Gy compared to IMPT. In most cases, V4000cGy and V5000cGy within ILBM and LSBM were significantly higher for IMPT plans compared to VMAT plans. CONCLUSIONS: BMS plans are achievable with VMAT and IMPT without compromising target coverage or OARs constraints. IMPT plans were overall better at reducing mean and NTCP for HT3+ as well as low dose volumes to BM. However, IMPT had larger high dose volumes within LSBM and ILBM. Further studies are warranted to evaluate the clinical implications of these findings.
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Neoplasias da Próstata , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Masculino , Medula Óssea , Linfonodos , Órgãos em Risco , Pelve , Neoplasias da Próstata/radioterapia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos RetrospectivosRESUMO
The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Antígeno Prostático Específico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Radioisótopos de Gálio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Prostatectomia , Terapia de Salvação , Recidiva Local de Neoplasia/patologiaRESUMO
(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6-649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9-21.6 h), representing 50% (range: 8-90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1-17 h), representing 38% (range: 13-71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.
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Mesotelioma Maligno , Neoplasias , HumanosRESUMO
Background: The European Society for Radiotherapy & Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) panel on prostate bed delineation reflected on macroscopic local recurrences in patients referred for postoperative radiotherapy (PORT), a challenging situation without standardized approach, and decided to propose a consensus recommendation on target volume selection and definition. Methods: An ESTRO ACROP contouring consensus panel consisting of 12 radiation oncologists and one radiologist, all with subspecialty expertise in prostate cancer, was established. Participants were asked to delineate the prostate bed clinical target volumes (CTVs) in two separate clinically relevant scenarios: a local recurrence at the seminal vesicle bed and one apically at the level of the anastomosis. Both recurrences were prostate-specific membrane antigen (PSMA)-avid and had an anatomical correlate on magnetic resonance imaging (MRI). Participants also answered case-specific questionnaires addressing detailed recommendations on target delineation. Discussions via electronic mails and videoconferences for final editing and consensus were performed. Results: Contouring of the two cases confirmed considerable variation among the panelists. Finally, however, a consensus recommendation could be agreed upon. Firstly, it was proposed to always delineate the entire prostate bed as clinical target volume and not the local recurrence alone. The panel judged the risk of further microscopic disease outside of the visible recurrence too high to safely exclude the rest of the prostate bed from the CTV. A focused, "stereotactic" approach should be reserved for re-irradiation after previous PORT. Secondly, the option of a focal boost on the recurrence was discussed. Conclusion: Radiation oncologists are increasingly confronted with macroscopic local recurrences visible on imaging in patients referred for postoperative radiotherapy. It was recommended to always delineate and irradiate the entire prostate bed, and not the local recurrence alone, whatever the exact location of that recurrence. Secondly, specific dose-escalation on the macroscopic recurrence should only be considered if an anatomic correlate is visible. Such a focal boost is probably feasible, provided that OAR constraints are prioritized. Possible dose is also dependent on the location of the recurrence. Its potential benefit should urgently be investigated in prospective clinical trials.
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Purpose/Objective: Radiotherapy to the prostate bed is a potentially curative salvage option after radical prostatectomy. Although prostate bed contouring guidelines are available in the literature, important variabilities exist. The objective of this work is to provide a contemporary consensus guideline for prostate bed delineation for postoperative radiotherapy. Methods: An ESTRO-ACROP contouring consensus panel consisting of 11 radiation oncologists and one radiologist, all with known subspecialty expertise in prostate cancer, was established. Participants were asked to delineate the prostate bed clinical target volumes (CTVs) in 3 separate clinically relevant scenarios: adjuvant radiation, salvage radiation with PSA progression, and salvage radiation with persistently elevated PSA. These cases focused on the presence of positive surgical margin, extracapsular extension, and seminal vesicles involvement. None of the cases had radiographic evidence of local recurrence on imaging. A single computed tomography (CT) dataset was shared via FALCON platform and contours were performed using EduCaseTM software. Contours were analyzed qualitatively using heatmaps which provided a visual assessment of controversial regions and quantitatively analyzed using Sorensen-Dice similarity coefficients. Participants also answered case-specific questionnaires addressing detailed recommendations on target delineation. Discussions via electronic mails and videoconferences for final editing and consensus were performed. Results: The mean CTV for the adjuvant case was 76 cc (SD = 26.6), salvage radiation with PSA progression was 51.80 cc (SD = 22.7), and salvage radiation with persistently elevated PSA 57.63 cc (SD = 25.2). Compared to the median, the mean Sorensen-Dice similarity coefficient for the adjuvant case was 0.60 (SD 0.10), salvage radiation with PSA progression was 0.58 (SD = 0.12), and salvage radiation with persistently elevated PSA 0.60 (SD = 0.11). A heatmap for each clinical scenario was generated. The group agreed to proceed with a uniform recommendation for all cases, independent of the radiotherapy timing. Several controversial areas of the prostate bed CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences where the panel achieved consensus on the prostate bed CTV to be used as a novel guideline for postoperative prostate cancer radiotherapy. Conclusion: Variability was observed in a group formed by experienced genitourinary radiation oncologists and a radiologist. A single contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in prostate bed delineation, independent of the indication.There is important variability in existing contouring guidelines for postoperative prostate bed (PB) radiotherapy (RT) after radical prostatectomy. This work aimed at providing a contemporary consensus guideline for PB delineation. An ESTRO ACROP consensus panel including radiation oncologists and a radiologist, all with known subspecialty expertise in prostate cancer, delineated the PB CTV in 3 scenarios: adjuvant RT, salvage RT with PSA progression, and salvage RT with persistently elevated PSA. None of the cases had evidence of local recurrence. Contours were analysed qualitatively using heatmaps for visual assessment of controversial regions and quantitatively using Sorensen-Dice coefficient. Case-specific questionnaires were also discussed via e-mails and videoconferences for consensus. Several controversial areas of the PB CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences. Finally, a contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in PB delineation, independent of the indication.
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The utilization of multi-parametric MRI (mpMRI) in clinical decisions regarding prostate cancer patients' management has recently increased. After biopsy, clinicians can assess risk using National Comprehensive Cancer Network (NCCN) risk stratification schema and commercially available genomic classifiers, such as Decipher. We built radiomics-based models to predict lesions/patients at low risk prior to biopsy based on an established three-tier clinical-genomic classification system. Radiomic features were extracted from regions of positive biopsies and Normally Appearing Tissues (NAT) on T2-weighted and Diffusion-weighted Imaging. Using only clinical information available prior to biopsy, five models for predicting low-risk lesions/patients were evaluated, based on: 1: Clinical variables; 2: Lesion-based radiomic features; 3: Lesion and NAT radiomics; 4: Clinical and lesion-based radiomics; and 5: Clinical, lesion and NAT radiomic features. Eighty-three mpMRI exams from 78 men were analyzed. Models 1 and 2 performed similarly (Area under the receiver operating characteristic curve were 0.835 and 0.838, respectively), but radiomics significantly improved the lesion-based performance of the model in a subset analysis of patients with a negative Digital Rectal Exam (DRE). Adding normal tissue radiomics significantly improved the performance in all cases. Similar patterns were observed on patient-level models. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients' risk using combined clinical-genomic classification.
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BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572â545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.
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Neoplasias da Próstata , Masculino , Humanos , Estados Unidos/epidemiologia , Medição de Risco/métodos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Antígeno Prostático Específico , Próstata/cirurgia , Próstata/patologia , GenômicaRESUMO
BACKGROUND: To assess the impact of systematic setup and range uncertainties for robustly optimized (RO) intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans in patients with localized prostate cancer. METHODS: Twenty-six localized prostate patients previously treated with VMAT (CTV to PTV expansion of 3-5 mm) were re-planned with RO-IMPT with 3 mm and 5 mm geometrical uncertainties coupled with 3% range uncertainties. Robust evaluations (RE) accounting for the geometrical uncertainties of 3 and 5 mm were evaluated for the IMPT and VMAT plans. Clinical target volume (CTV), anorectum, and bladder dose metrics were analyzed between the nominal plans and their uncertainty perturbations. RESULTS: With geometric uncertainties of 5 mm and accounting for potential inter-fractional perturbations, RO-IMPT provided statistically significant (p < 0.05) sparing at intermediate doses (V4000cGy) to the anorectum and bladder and high dose sparring (V8000cGy) to the bladder compared to VMAT. Decreasing the RO and RE parameters to 3 mm improved IMPT sparing over VMAT at all OAR dose levels investigated while maintaining equivalent coverage to the CTV. CONCLUSIONS: For localized prostate treatments, if geometric uncertainties can be maintained at or below 3 mm, RO-IMPT provides clear dosimetric advantages in anorectum and bladder sparing compared to VMAT. This advantage remains even under uncertainty scenarios. As geometric uncertainties increase to 5 mm, RO-IMPT still provides dosimetric advantages, but to a smaller magnitude.