RESUMEN
PURPOSE: Stereotactic body radiation therapy (SBRT) is an emerging option for localized prostate cancer. However, there are no standard dosimetric guidelines, and normal tissue tolerances for extreme hypofractionation are not well defined. We analyzed dosimetric correlations with patient-reported urinary and bowel quality of life (QOL) on a prospective trial. METHODS AND MATERIALS: Patients with low- or intermediate-risk prostate cancer from 18 institutions were enrolled on a phase 2 trial from 2007 to 2012 and treated using robotic SBRT to 38 Gy in 4 fractions on consecutive days. No androgen deprivation was used. Patients received simulation with Foley catheter for urethral delineation. The clinical target volume was prostate (low-risk patients) or prostate plus 1 cm of proximal seminal vesicles (intermediate-risk patients). Multiple dosimetric measures for urethra, bladder, and rectum were prospectively recorded. QOL using the Expanded Prostate Cancer Index Composite was assessed before and after treatment at protocol-specific time points. Linear regression was used to assess factors associated with QOL at 1 month and 2 years. RESULTS: A total of 259 patients were enrolled. QOL data were available for 98%, 96%, and 84% at baseline, 1 month, and 2 years, respectively. Median age was 69 years. Prior transurethral resection of the prostate and clinical target volume size were associated with 2-year urinary incontinence. There was a trend toward worse 2-year obstruction/irritation in older patients on multivariable analysis. Bladder and urethral doses were not associated with either 1-month or 2-year urinary QOL. In contrast, rectum maximum dose was associated with both 1-month and 2-year bowel QOL. At 2 years, the proportion with moderate or big overall bowel problems (as defined by Expanded Prostate Cancer Index Composite-26) was significantly higher in patients with rectum maximum dose greater than versus less than the median 37.4 Gy (11% vs 2%, Fisher's exact test P = .008). CONCLUSIONS: These results provide novel data that contribute to a better understanding of patient and dosimetric factors associated with adverse QOL effects from prostate SBRT.
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Tracto Gastrointestinal/efectos de la radiación , Neoplasias de la Próstata/radioterapia , Calidad de Vida , Radiocirugia/efectos adversos , Sistema Urogenital/efectos de la radiación , Anciano , Tracto Gastrointestinal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/fisiopatología , Radiometría , Incontinencia Urinaria/etiología , Sistema Urogenital/fisiopatologíaRESUMEN
BACKGROUND: Stereotactic body radiation therapy is an emerging treatment for prostate cancer (PC), with potential biological and oncologic advantages. A well-established radiation dosing schedule (38Gy in 4 fractions) has shown excellent long-term efficacy in high-dose-rate (HDR) brachytherapy. OBJECTIVE: To report 5-yr efficacy, toxicity, and quality-of-life (QOL) outcomes of a novel 4-d SBRT regimen. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm prospective phase 2 trial involving 259 patients with low- or intermediate-risk PC treated at 18 US centers from December 2007 to February 2012. The median follow-up was 5yr (interquartile range 37-85mo). INTERVENTION: SBRT with 38Gy in four fractions; radiation plans mimicked HDR brachytherapy dosimetry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured freedom from biochemical recurrence (BCR) and assessed toxicities using the Common Terminology Criteria for Adverse Events v3.0 and QOL using the Expanded Prostate Cancer Index Composite. RESULTS AND LIMITATIONS: The 5-yr BCR-free rates were 100% and 88.5% for patients with low- and intermediate-risk PC, respectively. The cumulative 5-yr grade 2, 3, and 4 toxicity rates were 12.4%, 1.9%, and 0.4% for urinary, and 3.4%, 0%, and 0% for gastrointestinal toxicities, respectively. The median baseline prostate-specific antigen (PSA) level of 5.12ng/ml decreased to 0.1ng/ml by ≥42mo. QOL scores decreased at 1mo but returned to baseline by 6mo, with a later decline (≥24mo) in the urinary continence domain (pad use was 2% at baseline and 10% at 5yr), and lower sexual potency over time. Comparative outcomes versus other types of radiotherapy are difficult because the trial was not randomized. CONCLUSIONS: This regimen yields a high rate of BCR-free survival, with a very low median PSA nadir suggesting prostate ablation. For properly selected patients with low- or intermediate-risk PC who choose SBRT, this treatment regimen is effective. PATIENT SUMMARY: This potent four-treatment stereotactic body radiotherapy regimen appears to be effective for patients with early prostate cancer.
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Neoplasias de la Próstata/radioterapia , Radiocirugia/efectos adversos , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/mortalidad , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. METHODS/MATERIALS: The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. RESULTS: The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, pâ=â0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, pâ=â0.24), respectively, favoring the variant. CONCLUSIONS: The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
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Neoplasias Endometriales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Mutación/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Neoplasias Endometriales/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Metástasis Linfática/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas Proto-Oncogénicas p21(ras) , Factores de RiesgoRESUMEN
BACKGROUND: Due to its short duration of therapy and low rates of local recurrence, women undergoing breast conservation are increasingly opting for partial breast irradiation with the MammoSite (Cytyc/Hologic) catheter. In early follow-up studies, few complications were reported. Few data, however, exist regarding longer-term complications. We compared the long-term local toxicities of MammoSite partial breast irradiation with those resulting from whole breast radiation. STUDY DESIGN: This was a retrospective study performed in a single academic medical center. All patients who underwent breast-conserving surgery between 2003 and 2008, who met institutional criteria for brachytherapy, were included. We compared women treated with MammoSite with patients treated with whole breast radiation therapy (WBRT). Endpoints included incidence of palpable masses at the lumpectomy site, telangiectasias, and local recurrence. RESULTS: Seventy-one MammoSite patients and 245 WBRT patients were well matched with regard to clinical characteristics. Median follow-up was 4 years. A palpable mass developed at the site of lumpectomy in 27% of the MammoSite patients compared with 7% of the WBRT patients (p < 0.0001). Telangiectasias developed more frequently in the MammoSite group than in the WBRT group (24% vs 4%, p < 0.001). Forty-two percent of patients treated with MammoSite developed a palpable mass, telangectasia, or both. CONCLUSIONS: Palpable masses and telangiectasias are frequent long-term complications after MammoSite brachytherapy and occur at a significantly higher rate after MammoSite brachytherapy than after WBRT. This increased rate of long-term local toxicity should be considered when counseling women on options for adjuvant radiation therapy after breast-conserving surgery.
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Braquiterapia/efectos adversos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Telangiectasia/etiologíaRESUMEN
PURPOSE: To review outcomes with intensity-modulated radiation therapy (IMRT) in the community setting for the treatment of nasopharyngeal and oropharyngeal cancer. METHODS AND MATERIALS: Between April 2003 and April 2007, 69 patients with histologically confirmed cancer of the nasopharynx and oropharynx underwent IMRT in our practice. The primary sites included nasopharynx (11), base of tongue (18), and tonsil (40). The disease stage distribution was as follows: 2 Stage I, 11 Stage II, 16 Stage III, and 40 Stage IV. All were treated with a simultaneous integrated boost IMRT technique. The median prescribed doses were 70 Gy to the planning target volume, 59.4 Gy to the high-risk subclinical volume, and 54 Gy to the low-risk subclinical volume. Forty-five patients (65%) received concurrent chemotherapy. Toxicity was graded according to the Radiation Therapy Oncology Group toxicity criteria. Progression-free and overall survival rates were estimated with the Kaplan-Meier product-limit method. RESULTS: Median duration of follow-up was 18 months. The estimated 2-year local control, regional control, distant control, and overall survival rates were 98%, 100%, 98%, and 90%, respectively. The most common acute toxicities were dermatitis (32 Grade 1, 32 Grade 2, 5 Grade 3), mucositis (8 Grade 1, 33 Grade 2, 28 Grade 3), and xerostomia (0 Grade 1, 29 Grade 2, 40 Grade 3). CONCLUSIONS: Intensity-modulated radiotherapy in the community setting can be accomplished safely and effectively. Systematic internal review systems are recommended for quality control until sufficient experience develops.
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Servicios de Salud Comunitaria , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Orofaríngeas/radioterapia , Radiodermatitis/etiología , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Oregon , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: A phase II study was completed by the RTOG to assess the feasibility, safety, toxicity, and patterns of recurrence and survival when chemotherapy was combined with adjuvant radiation for patients with high-risk endometrial cancer. MATERIALS AND METHODS: Pathologic requirements included grade 2 or 3 endometrial adenocarcinoma with either >50% myometrial invasion, cervical stromal invasion, or pelvic-confined extrauterine disease. Radiation included 45 Gy in 25 fractions to the pelvis along with cisplatin (50 mg/m(2)) on days 1 and 28. Vaginal brachytherapy was performed after the external beam radiation. Four courses of cisplatin (50 mg/m(2)) and paclitaxel (175 mg/m(2)) were given at 4-week intervals following completion of radiotherapy. RESULTS: Forty-six patients were entered between 10/97 and 4/99. Follow-up times range from 6.8 to 72 months with a median of 4.3 years. Maximum late toxicity was grade 1 in 16%, grade 2 in 41%, grade 3 in 16%, and grade 4 in 5%. At 4 years pelvic, regional and distant recurrence rates are 2%, 2%, and 19%, respectively. Overall survival and disease-free survival (DFS) rates at 4 years are 85% and 81%, respectively. Four-year rates for survival and DFS for Stage III patients are 77% and 72%, respectively. There have been no recurrences for patients with stage IC, IIA, or IIB. CONCLUSION: Local-regional control is excellent following combined modality treatment in all patients suggesting additive effects of chemotherapy and radiation. Distant metastases continue to occur in more advanced staged patients. This regimen appears reasonable to be tested for efficacy in randomized studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Histerectomía , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Radioterapia Adyuvante/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE: Patients with completely resected high-risk endometrial cancer have a risk of disease recurrence even with the addition of adjuvant pelvic radiotherapy (RT). A Phase II study was completed by the Radiation Therapy Oncology Group to assess the safety and toxicity of chemotherapy when combined with pelvic RT for these patients. METHODS AND MATERIALS: Eligibility requirements included a total abdominal hysterectomy and bilateral salpingo-oophorectomy with Grade 2 or 3 endometrial adenocarcinoma with >50% myometrial invasion, stromal invasion of the cervix, or pelvic-confined extrauterine disease. This study was designed to administer 4500 cGy in 25 fractions to the pelvis, along with cisplatin (50 mg/m(2)) on Days 1 and 28. Vaginal brachytherapy with a low-dose-rate applicator (1 x 20 Gy to the surface) or high-dose-rate applicator (3 x 6 Gy to the surface) was performed after external beam RT. Four courses of cisplatin (50 mg/m(2)) and paclitaxel (175 mg/m(2)) were given at 4-week intervals after RT completion. RESULTS: Forty-six patients were entered between October 1997 and April 1999. Two patients were ineligible (one with previous bladder cancer and one who had undergone surgery >8 weeks before the start of RT). Follow-up ranged from 6.9 to 48.8 months (median, 28.7 months). The disease was Stage III, II, and I in 66%, 16%, and 18% of patients, respectively. Two patients were not assessable because of incomplete treatment data. The protocol completion rate was 98% (41 of 42 assessable patients). Acute toxicity during RT/chemotherapy was Grade 1 in 27%, Grade 2 in 43%, Grade 3 in 27%, and Grade 4 in 2%. During adjuvant chemotherapy, the toxicity was Grade 1 in 7%, Grade 2 in 7%, Grade 3 in 21%, and Grade 4 in 62%. Severe toxicity was primarily hematologic. Chronic toxicity was Grade 1 in 20%, Grade 2 in 39%, Grade 3 in 16%, and Grade 4 in 2%, including 1 patient with a Grade 4 small bowel complication. At 24 months, the pelvic recurrence, regional recurrence, distant recurrence, disease-free survival, and overall survival rate was 2%, 3%, 17%, 83%, and 90%, respectively. CONCLUSION: This treatment protocol demonstrated an excellent treatment completion rate and expected toxicity. Longer follow-up is needed to assess the outcome. To assess the efficacy of this adjuvant treatment program, a Phase III trial (Radiation Therapy Oncology Group 9905) was designed with high-risk uterine-confined disease to be randomized between pelvic RT alone and pelvic RT with chemotherapy.
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Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Paclitaxel/administración & dosificación , Cooperación del Paciente , Dosificación Radioterapéutica , Radioterapia Adyuvante/efectos adversos , Recurrencia , Análisis de SupervivenciaRESUMEN
OBJECTIVE: The goal of this study was to determine the maximal tolerated dose (MTD) of topotecan given with external-beam radiotherapy in advanced cervical cancer. METHODS: A prospective Phase I trial of topotecan given with standard external-beam radiotherapy was performed in patients with advanced squamous cell carcinoma of the cervix. Patients were treated with a starting dose of 0.5 mg/m(2) and escalated by 0.25 mg/m(2). Nine patients were treated. Hematologic and nonhematologic toxicity were measured. RESULTS: Patients were treated with 1.0 mg/m(2) daily for 5 days on Days 1-5 and 22-26 concomitantly with radiotherapy without significant toxicity. Grade III anemia in one case and Grade II leukopenia in two cases were seen in the three patients at this dose level. Dose-limiting toxicity was not reached. CONCLUSION: Topotecan can be safely administered at a dose of 1.0 mg/m(2) during external-beam radiotherapy for advanced cervical cancer.