Ethnic difference in risk of toxicity in prostate cancer patients treated with dynamic arc radiation therapy.

AIMS AND BACKGROUND: The objective of this study was to assess the influence of ethnicity on toxicity in patients treated with dynamic arc radiation therapy (ART) for prostate cancer (PC). METHODS: From June 2006 to May 2012, 162 cT1-T3 cN0 cM0 PC patients were treated with ART (primary diagnosis, n = 125; post-prostatectomy/brachytherapy biochemical recurrence, n = 26; adjuvant post-prostatectomy, n = 11) at 2 institutions. Forty-five patients were Latin Americans and 117 were Europeans. The dose prescribed to the prostate ranged between 68 Gy and 81 Gy. RESULTS: The median age was 69 years (range 43-87 years). The median follow-up was 18 months (range 2-74 months). Overall, only 3 patients died, none due to a cancer-related cause. Biochemical recurrence was seen in 7 patients. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 19.7% and 17%, respectively. Only 1 patient experienced acute grade 3 GI toxicity, whereas 11 patients (6.7%) experienced acute grade 3 GU toxicity. Multivariate analysis showed that undergoing whole pelvic lymph node irradiation was associated with a higher grade of acute GI toxicity (OR: 3.46; p = 0.003). In addition, older age was marginally associated with a higher grade of acute GI toxicity (OR: 2.10; p = 0.074). Finally, ethnicity was associated with acute GU toxicity: Europeans had lower-grade toxicity (OR: 0.27; p = 0.001). CONCLUSIONS: Our findings suggest an ethnic difference in GU toxicity for PC patients treated with ART. In addition, we found that ART is associated with a very low risk of severe toxicity and a low recurrence rate.

Image-guided radiation therapy based on helical tomotherapy in prostate cancer: minimizing toxicity.

BACKGROUND: We report the clinical results and prognostic factors of image-guided radiation therapy (RT) with helical tomotherapy (HT) for localized and recurrent prostate cancer (PC). PATIENTS AND METHODS: We evaluated 70 patients with PC (primary diagnosis, n = 48; adjuvant, n = 5; salvage, n = 17) treated with HT from May 2006 through January 2011. The dose prescribed to the prostate/surgical bed ranged between 60 and 78 Gy. Potential risk factors for genitourinary (GU) and gastrointestinal (GI) toxicity were assessed. RESULTS: The median age was 68 years (range 51-87 years). The median follow-up was 37 months (range 3-74 months). The rates of acute grade 2 GI and GU toxicities were 10 and 13%, respectively. Only 1 patient experienced acute grade 3 GU toxicity. The rates of late grade ≥ 2 GI and GU toxicities were 1% each. Multivariate analysis showed an association between rectum mean dose > median (39 Gy) and bladder median dose > median (46 Gy) with a higher grade of acute GI (p = 0.017) and GU (p = 0.019) toxicity, respectively. Additionally, older age was associated with late GU toxicity (p = 0.026). CONCLUSION: Toxicity with HT is low and is associated with higher median/mean doses in organs at risk as well as with older age. A prospective validation would be necessary to confirm these results.

Hypofractionated helical tomotherapy using 2.5-2.6 Gy daily fractions for localized prostate cancer.

BACKGROUND: The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. MATERIALS AND METHODS: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49-87) and the median follow-up 11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively). CONCLUSION: Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.

Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity.

BACKGROUND: Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. METHODS: In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. RESULTS: The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. CONCLUSION: HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.

Stereotactic radiosurgery in pituitary adenomas: long-term single institution experience and role of the hypothalamic-pituitary axis.

Stereotactic radiosurgery (SRS) is an effective treatment for incompletely resected or recurrent pituitary adenomas characterized by high rates of local control and endocrinological remission. The SRS-associated morbidity is usually considered minimal, but could not be neglected. It is mainly related to new pituitary hormone deficit, and seemingly caused by un-intentional inclusion of the hypothalamus, pituitary stalk and gland in the high-dose irradiation area. We report long-term clinical outcomes of 30 pituitary adenoma patients who received SRS in our institution. Dose was generally prescribed to the 90% isodose line and ranged from 10 to 16 Gy (mean and median 14 Gy). Selection of prescription dose was based on a tumor location and proximity to adjacent radiation-sensitive structures and previous radiotherapy. The length of follow-up varied from 15 to 230 months (mean 102.6 months, median 90 months). Overall, in 28 patients (93%) control of tumor growth was observed during the followup. In 19 patients (63%) tumor size was considered stable after SRS, in 9 patients (30%) tumor reduced in size and in 2 patients (7%) tumor progression was observed. Among 26 patients with functioning pituitary adenomas 17 patients (65,4%) had normalization and 4 patients (15,3%) had improvement of endocrinological function. Persistent hypersecretion was observed in 5 patients (19,3%) with functioning pituitary adenomas. New hypopituitarism after SRS treatment was observed in 4 patients (13.3%). The median maximum dose to hypothalamus, pituitary stalk and pituitary gland was 2.33 Gy (range 0.78-6.22 Gy), 11.20 Gy (range 3.17-15.49 Gy) and 12.83 Gy (range 5.00-15.24 Gy), respectively. SRS allows to effectively control tumor growth in 90-100% of patients and in the great part of patients a relatively rapid endocrinological remission is observed. Doses to the structures of hypothalamic-pituitary axis might have influence on the development of radiation-induced hypopituitarism. Every effort should be made to spare these structures as much as possible.

[Fractionated stereotactic-guided radiotherapy in the treatment of pituitary adenomas]. / Radioterapia estereotáxica fraccionada en adenomas de hipófisis: resultados y factores pronósticos.

AIMS: To evaluate the survival rates, prognostic factors and adverse events in patients with pituitary adenomas following fractionated stereotactic-guided radiotherapy (FSRT). MATERIAL AND METHODS: Fifty-six patients with pituitary adenomas were treated with FSRT; 23 patients (41.1%) had primary adenomas, 33 had recurrent disease; 24 (42.9%) with non-functional and 32 (57.1%) with functional adenomas. Using conventional fractionation, median total dose administered was 54 Gy (range: 24-56 Gy). RESULTS: The median follow-up was 51 months (range: 9-102) and, at the time of analysis, 49 patients were alive and disease-free, 1 patient was alive with reduced visual acuity and biochemical indications of recurrence, 2 patients had died from the disease and 1 patient had died from unrelated causes. Overall survival was 94% (50/53) and overall local tumour control was 92% (49/53). Univariate analysis indicated hormonal secretion (ACTH) and previous radiotherapy as being statistically significant. Fourteen patients (25%) had minor side-effects during treatment and 3 patients (5.4%) had late-onset events; 2 with optical neuropathy (both patients had other relevant co-existing diseases) and 1 patient had brain necrosis (re-irradiation). CONCLUSION: Fractionated stereotactic-guided radiotherapy is an effective modality for the treatment of pituitary adenomas. Care is required in patients with co-morbidities and/or previously-irradiated recurrent tumour so as to minimise late-onset secondary effects.

Radioterapia estereotáxica fraccionada en adenomas de hipófisis: resultados y factores pronósticos / Fractionated stereotactic-guided radiotherapy in the treatment of pituitary adenomas

Introducción. Se analizan retrospectivamente la supervivencia global (SG), control local, factores pronóstico y toxicidad, de pacientes con adenoma de hipófisis tratados con radioterapia estereotáxica fraccionada (REF). Material y métodos. Entre mayo de 1994 y junio de 2001 se trataron 56 pacientes con adenomas de hipófisis, 23 (41,1%) primarios y 33 recidivas. Veinticuatro (42,9%) casos fueron adenomas no funcionantes, y 32 (57,1%) funcionantes. La mediana de dosis administrada fue 54 Gy (rango 24-56 Gy), 2 Gy/día, 5 días/semana. Resultados. Con un seguimiento de 51 meses (9-102 meses), al cierre del estudio, 49 pacientes están vivos sin evidencia de enfermedad, una paciente viva, con pérdida de visión y progresión hormonal, 2 pacientes han fallecido con progresión y uno falleció por otra causa. La supervivencia global fue de 94% (50/53), con una supervivencia libre de fallo del 92% (49/53). En análisis univariado sólo el tipo de hormona secretada (ACTH) y la irradiación previa resultaron de mal pronóstico. Catorce pacientes (25%) presentaron síntomas leves de toxicidad aguda durante la radioterapia estereotáxica fraccionada y 3 (5,4%) desarrollaron toxicidad tardía, neuropatía óptica (2 pacientes, multipatología asociada) y radionecrosis (1 paciente, reirradiación). Conclusiones. La radioterapia estereotáxica fraccionada es eficaz para adenomas de hipófisis, aunque es preciso valorar individualmente a aquellos pacientes con patologías concomitantes, o con tratamientos de radioterapia previa, con objeto de minimizar la aparición de efectos adversos a largo plazo

Aims. To evaluate the survival rates, prognostic factors and adverse events in patients with pituitary adenomas following fractionated stereotactic-guided radiotherapy (FSRT). Material and methods. Fifty-six patients with pituitary adenomas were treated with FSRT; 23 patients (41.1%) had primary adenomas, 33 had recurrent disease; 24 (42.9%) with non-functional and 32 (57.1%) with functional adenomas. Using conventional fractionation, median total dose administered was 54 Gy (range: 24-56 Gy). Results. The median follow-up was 51 months (range: 9-102) and, at the time of analysis, 49 patients were alive and disease-free, 1 patient was alive with reduced visual acuity and biochemical indications of recurrence, 2 patients had died from the disease and 1 patient had died from unrelated causes. Overall survival was 94% (50/53) and overall local tumour control was 92% (49/53). Univariate analysis indicated hormonal secretion (ACTH) and previous radiotherapy as being statistically significant. Fourteen patients (25%) had minor side-effects during treatment and 3 patients (5.4%) had late-onset events; 2 with optical neuropathy (both patients had other relevant co-existing diseases) and 1 patient had brain necrosis (re-irradiation). Conclusion. Fractionated stereotactic-guided radiotherapy is an effective modality for the treatment of pituitary adenomas. Care is required in patients with co-morbidities and/or previously-irradiated recurrent tumour so as to minimise late-onset secondary effects