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ABSTRACT: Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases.
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Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/patología , Manejo de la Enfermedad , Terapia Combinada/métodos , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , FemeninoRESUMEN
BACKGROUND: We previously reported that for men undergoing combined androgen deprivation therapy (ADT) and radiation therapy (RT) for prostate cancer, substitution of LHRH-agonists with 5-α- reductase inhibitors (5-ARIs) led to improved preservation of 6-month hormonal quality of life (hQOL). With longer term follow-up, we evaluated disease control. METHODS: In this non-randomized trial, men with unfavorable intermediate or high-risk prostate cancer, aged ≥70 years or with Charlson Comorbidity Index ≥2, were treated with RT (78-79.2 Gy in 39-44 fractions) and either oral ADT (oADT; 5-ARI with antiandrogen) or standard of care ADT (SOC; leuprolide with antiandrogen) for up to 28 months. The primary endpoint was EPIC hQOL; secondary endpoints included biochemical control and survival as well as changes in cholesterol and hemoglobin levels. RESULTS: Between 2011 and 2018, 70 men were enrolled (40 in oADT; 30 in SOC). Median follow-up was 65 months [IQR 36-94]. Five-year freedom from biochemical failure for oADT and SOC was 89% versus 86%, disease free survival was 62% versus 69%, cancer-specific survival was 100% versus 96%, and overall survival was 70% versus 81% (all P>.1). Testosterone (2 mo through 3 yr) and hemoglobin levels (2 mo through 2 yr) were higher, and cholesterol levels (1 yr) were lower in the oADT groups (all P < .05). CONCLUSIONS: In this non-randomized study, men treated with combined RT and oADT had better preservation of hQOL and comparable 5-year disease outcomes to men treated with SOC. Eugonadal testosterone with this approach may yield measurable benefits in cholesterol and hemoglobin levels.
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Inhibidores de 5-alfa-Reductasa , Antagonistas de Andrógenos , Hormona Liberadora de Gonadotropina , Neoplasias de la Próstata , Calidad de Vida , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/mortalidad , Anciano , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Andrógenos/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Leuprolida/administración & dosificación , Leuprolida/uso terapéutico , Resultado del Tratamiento , Estudios de Seguimiento , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
INTRODUCTION: Many patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. MATERIALS AND METHODS: Patients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/- pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. CONCLUSION: Maximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.
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Neoplasias de la Vejiga Urinaria , Vejiga Urinaria , Humanos , Anciano , Capecitabina/efectos adversos , Terapia Combinada , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Cisplatino/uso terapéutico , Cistectomía , Invasividad NeoplásicaRESUMEN
PURPOSE: External beam radiation therapy to the prostate is typically delivered after verification of prostatic position with image guidance. Prostate motion can occur during the delivery of each radiation treatment between the time of localization imaging and completion of treatment. The objective of this work is to review the literature on intrafraction motion (IFM) of the prostate during radiation therapy and offer clinical recommendations on management. METHODS AND MATERIALS: A comprehensive literature review was conducted on prostate motion during prostate cancer radiation therapy. Information was organized around 3 key clinical questions, followed by an evidence-based recommendation. RESULTS: IFM of the prostate during radiation therapy is typically ≤3 mm and is unlikely to compromise prostate dosimetry to a clinically meaningful degree for men treated in a relatively short treatment duration with planning target volume (PTV) margins of ≥3 to 5 mm. IFM of 5 mm or more has been observed in up to â¼10% of treatment fractions, with limited dosimetric effect related to the infrequency of occurrence and longer fractionation of therapy. IFM can be monitored in continuous or discontinuous fashion with a variety of imaging platforms. Correction of IFM may have the greatest value when tighter PTV margins are desired (such as with stereotactic body radiation therapy or intraprostatic nodule boosting), ultrahypofractionated courses, or when treatment time exceeds several minutes. CONCLUSIONS: This focused review summarizes literature and provides practical recommendations regarding IFM in the treatment of prostate cancer with external beam radiation therapy.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Movimiento (Física) , Fraccionamiento de la Dosis de Radiación , Dosificación RadioterapéuticaRESUMEN
PURPOSE: We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). METHODS: 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144-145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. RESULTS: Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2-24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. CONCLUSION: Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease.
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PURPOSE: Pelvic recurrence of rectal or anal cancers is associated with considerable morbidity and mortality. We report our initial experience with an aggressive intra-operative radiotherapy (IORT) program. METHODS: Patients with locally advanced or recurrent rectal or anal cancers considered to have a high likelihood of R1 or R2 resection after multi-disciplinary review underwent surgical excision and IORT using a high-dose-rate afterloader (Ir-192) and HAM applicator. Endpoints included local or distant recurrence, and acute and late toxicity graded using the American College of Surgeons (ACS) NSQIP and the LENT-SOMA scale. RESULTS: Twenty-one patients, largely with prior history of both pelvic external beam radiotherapy (EBRT, median 50.4 Gy) and surgical resection, underwent excision with IORT (median dose 12.5 Gy, range 10-15). Median follow-up was 20 months. Twelve (57%) patients had failure at the IORT site. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF at 1 year 75% for R0 vs 15% for R1/2, p = 0.0065) but not re-irradiation EBRT or IORT dose (p > 0.05). Twelve, 5, and 13 patients experienced local, regional, and distant failure, respectively; 3 (14%) patients were disease-free at last follow-up. The most frequent acute toxicity was sepsis/abscess (24%). One patient (5%) required a ureteral stent; no patients developed neuropathy attributable to IORT. CONCLUSIONS: In patients treated with excision and IORT for locally recurrent cancer, R0 resection is a critical determinant of local control. For patients with R1/2 resection, poor disease-free outcomes warrant consideration of a different treatment strategy.
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Neoplasias del Ano , Humanos , Neoplasias del Ano/radioterapia , Neoplasias del Ano/cirugíaRESUMEN
PURPOSE: Immunotherapy has emerged as a promising therapeutic option for advanced or unresectable hepatocellular carcinoma (HCC). However, survival remains poor with only a subset of patients deriving benefit. This trial investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in HCC. METHODS AND MATERIALS: In this multicenter phase 1 randomized trial, patients with advanced or unresectable HCC received liver SBRT (40 Gy in 5 fractions) followed by either nivolumab alone or nivolumab plus ipilimumab. The primary endpoint was dose-limiting toxicity occurring within 6 months of SBRT. Secondary endpoints included overall response rate, progression-free survival, overall survival (OS), distant disease control, and local control of the irradiated tumor. Disease status and response endpoints were assessed radiographically every 8 weeks until progression or initiation of nonprotocol therapy. Response was determined using both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and iRECIST. RESULTS: Fourteen patients were enrolled across 3 centers. Thirteen patients were evaluated for study endpoints. The study was closed early because of slow accrual. The median follow-up time was 42.7 months. Dose-limiting toxicities within 6 months occurred in 2 (15.4%) of 13 patients: 1 of 6 patients in the nivolumab arm (16.7%; 90% confidence interval [CI], 0.9%-58.2%) and 1 of 7 patients in the nivolumab plus ipilimumab arm (14.3%; 90% CI, 0.7%-52.1%). Grade 3 adverse events occurred in 8 (61.6%), 5 (71.4%), and 3 (50.0%) patients in the overall nivolumab plus ipilimumab and nivolumab cohorts. Grade 3 hepatotoxicity occurred in 4 (30.8%), 3 (42.9%), and 1 (16.7%) patients in the respective cohorts. Clinical outcomes favored the nivolumab plus ipilimumab arm compared with nivolumab alone, including an overall response rate of 57% (4 of 7 patients; 90% CI, 23%-87%) versus 0% (0 of 6 patients; 90% CI, 0%-39%), median progression-free survival of 11.6 months (90% CI, 4.5 months to not reached) versus 2.7 months (90% CI, 1.3-4.7 months), and median OS of 41.6 months (90% CI, 4.5 months to not reached) versus 4.7 months (90% CI, 2.0-16.2 months) (all P < .05). With combination immunotherapy, 3-year OS was 57% (90% CI, 23%-81%), with 2 patients alive after 42.7 months without progression and negative PET. CONCLUSIONS: In this first prospective trial investigating the combination of SBRT and immunotherapy for HCC, multimodal therapy demonstrated acceptable safety. SBRT with nivolumab plus ipilimumab compared favorably to outcomes of immunotherapy alone and warrants further investigation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Ipilimumab/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Nivolumab/uso terapéutico , Estudios Prospectivos , Inmunoterapia , Terapia Combinada/efectos adversosRESUMEN
PURPOSE: We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS: Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double-blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695). Random assignment (1:1) was stratified by center, surgical margin status (R0 v R1), PSA before salvage treatment (PSA ≥ 0.5 v < 0.5 ng/mL), and pathologic Gleason sum (7 v 8-10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6-70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis-free survival, and safety as determined by frequency and severity of adverse events. RESULTS: Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; P = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; Pinteraction = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; Pinteraction = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA v 53% placebo) and urinary frequency (40% ENZA v 49% placebo). CONCLUSION: SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Antagonistas de Andrógenos/efectos adversos , Terapia Recuperativa , Recurrencia Local de Neoplasia/tratamiento farmacológico , ProstatectomíaRESUMEN
There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.
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Neoplasias de la Vejiga Urinaria , Humanos , Terapia Combinada , Estadificación de Neoplasias , Invasividad Neoplásica/patología , Neoplasias de la Vejiga Urinaria/radioterapia , Cistectomía , Terapia NeoadyuvanteRESUMEN
OBJECTIVE: To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer. METHODS: The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R2, a measure of explained variation, was calculated using a multivariable model. RESULTS: Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume. CONCLUSION: Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Clasificación del Tumor , Próstata/patología , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/química , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patologíaRESUMEN
PURPOSE: Hematuria following post-prostatectomy radiotherapy (PPRT) is inadequately characterized. We performed a consecutive cohort study of patients treated with PPRT at our institution to characterize this complication including impact on patient-reported quality of life. MATERIALS AND METHODS: Patients with potential followup ≥4 years following PPRT were identified. Freedom from ≥grade 2 hematuria (FFG2H; macroscopic blood) was estimated using the Kaplan-Meier method. Predictors of ≥grade 2 hematuria (G2H) were assessed via log-rank tests and the Cox model. Urinary patient-reported quality of life by EPIC-26 (26-question Expanded Prostate Cancer Index Composite) was compared for patients with/without hematuria using mixed-effects regression. RESULTS: A total of 216 men received PPRT (median 68.4 Gy, IQR 68.0-68.4) from 2007 to 2016 at a median of 20 months (IQR 9-45) after prostatectomy. Median followup was 72 months (IQR 54-99). A total of 85 men developed hematuria, of whom 49 (58%) underwent cystoscopy, 13 (15%) required intervention and 26 (31%) experienced recurrent hematuria. Eight-year FFG2H was 55%. G2H was highest in men treated with anticoagulation/antiplatelet therapy (HR 3.24, p <0.001), men with bladder V65 Gy ≥43% (HR 1.97, p=0.004) and men with medication allergies (HR 1.73, p=0.049). Age <65 years (HR 0.81, p=0.374) and diabetes mellitus (HR 0.49, p=0.098) were not associated with G2H. Change in urinary continence (mean -3.5, 95% CI: 10.1, 3.1) and irritation/obstruction (mean -3.0, 95% CI: 5.8, -0.3) domain scores did not exceed the minimally clinically important difference for men with/without hematuria. CONCLUSIONS: Hematuria following PPRT is common, especially among men with medication allergies and those on anticoagulation/antiplatelet therapy; however, PPRT-related hematuria is typically self-limited. Limiting bladder V65 Gy may reduce PPRT-related hematuria.
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Hipersensibilidad , Neoplasias de la Próstata , Anciano , Anticoagulantes , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hematuria/epidemiología , Hematuria/etiología , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/cirugía , Incidencia , Masculino , Inhibidores de Agregación Plaquetaria , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Calidad de VidaRESUMEN
RATIONALE AND OBJECTIVES: To investigate whether pre-treatment quantitative multiparametric MRI can predict biochemical outcome of prostate cancer (PCa) patients treated with primary radiotherapy (RT). MATERIALS AND METHODS: Fifty-one patients with biopsy confirmed PCa underwent prostate multiparametric MRI on 3T MR scanner prior to RT. Thirty-seven men (73%) were treated with external beam RT alone, 12 men (24%) were treated with brachytherapy monotherapy, and two men (4%) were treated with external beam RT with brachytherapy boost. The index lesion was outlined by a radiologist and quantitative apparent diffusion coefficient (ADC), T2 and DCE parameters were measured. Biochemical failure was defined using the Phoenix criteria. RESULTS: After a median follow-up of 65 months, seven patients had biochemical failure. ADC had an area under the receiver operating characteristic curve of 0.71 for predicting RT outcome with significantly lower ADC (0.78 ± 0.17 vs 0.96 ± 0.26 µm2/ms, p = 0.04) of the index lesion in men with biochemical failure. Ideal ADC cutoff point (Youdens index) was 0.96 µm2/ms which had a sensitivity of 100% and specificity of 48% for predicting biochemical failure. Kaplan-Meier analysis showed that lower ADC values were associated with significantly lower freedom from biochemical failure (FFBF, p = 0.03, no failures out of 20 men if ADC ≥ 0.96 µm2/ms; seven of 31 with failures if ADC < 0.96 µm2/ms). On multivariable analysis, ADC was associated with FFBF (HR 0.96 per increase in ADC of 0.01 um2/ms [95% CI, 0.92-1.00]; p = 0.042) after accounting for National Comprehensive Cancer Network risk category (p = 0.064) and receipt of androgen deprivation therapy (p = 0.141). Quantitative T2 and DCE parameters were not associated with biochemical outcome. CONCLUSION: Our results suggest that quantitative ADC values of the index lesion may predict biochemical failure following primary radiotherapy in patients with PCa. Lower ADC values were associated with inferior biochemical control.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Antagonistas de Andrógenos , Imagen de Difusión por Resonancia Magnética , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS: The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS: The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.
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Antagonistas de Andrógenos , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Ciclo Celular , Estudios de Cohortes , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
The incidence of anal cancer in the United States has increased in recent years, primarily related to the increasing incidence of HPV-associated anal squamous cell carcinoma, which is estimated to represent 80%-95% of anal cancers. Similar to head and neck cancer, HPV association has been demonstrated to be a strong positive prognostic factor in patients with anal cancer. Encouraging results from a number of studies investigating treatment de-escalation for HPV-associated oropharyngeal cancer support the notion that similar attempts may be feasible in HPV-associated anal cancer; however, the data to support this hypothesis are currently lacking. Studies are needed to determine how, if at all, HPV status should impact the management of patients with anal cancer. This review summarizes the relationship between HPV association and outcomes for patients with anal cancer, and how HPV status may impact the treatment of patients with anal cancer going forward.
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Neoplasias del Ano , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Neoplasias del Ano/terapia , Quimioradioterapia , Humanos , Infecciones por Papillomavirus/complicaciones , Estados UnidosRESUMEN
BACKGROUND: Goals of care discussions (GOCD) are essential when counseling patients with cancer. Respective roles of radiation oncologists (RO) and medical oncologists (MO) in GOCD can be unclear. This study aims to clarify the dynamics and barriers to GOCD. METHODS: Five hundred and fifty-four ROs and 1604 MOs at NCI-designated comprehensive cancer centers were sent an anonymous electronic survey regarding demographics, opinions, training in GOCD, GOCD frequency, and three vignettes. Response formats were Yes/No, Likert-type, and free response. Chi-square and Wilcoxon rank-sum tests were performed. Likert-type scores were reported as median [interquartile range]. RESULTS: There were 76 (13.7%) RO and 153 (9.5%) MO who completed surveys. Sixty-three percent of RO and 66% of MO reported GOCD with > 50% of patients (p = 0.90). GOCD were initiated for declining performance status (74%) and poor life expectancy (69%). More MO (42%) received formal GOCD training compared to RO (18%) (p < 0.01). MO were more comfortable conducting GOCD than RO (p < 0.01). RO-conducted GOCD were rated to be less important by MO compared to RO (p < 0.05). Thirty-six percent of MO reported being "not at all" or "somewhat" comfortable with RO-conducted GOCD. RO-initiated GOCD with new patients were rated less appropriate by RO compared to MO perceptions of RO-initiated GOCD (p < 0.01). CONCLUSIONS: While MO and RO conduct GOCD with similar frequency, MO are more comfortable conducting GOCD and are more likely to have formal training. MO rate importance of RO involvement lower than RO. Further research is needed to understand interdisciplinary dynamics that may impact GOCD and subsequent patient care outcomes.