Intensity-modulated radiotherapy versus radical prostatectomy in patients with localized prostate cancer: long-term follow-up.

BACKGROUND: The objective of this work was to assess the overall survival, cause-specific survival and biochemical failure-free survival of a contemporary cohort of patients with localized prostate cancer (PCa) treated with intensity-modulated radiation therapy (IMRT) or radical prostatectomy (RP). METHODS: We did a retrospective cohort study of our institution's registry of patients undergoing either IMRT or RP between January 1999 and March 2010, and assessed Prostate Specific Antigen (PSA), age at diagnosis, Gleason score, and digital rectal examination. Two groups were separated according to RP or IMRT treatment and these groups were in turn divided into risk groups according to the D'Amico classification. Overall survival (OS), cause-specific survival (CSS), mortality from other causes (MOC), and biochemical disease-free survival (BDFS) were assessed. RESULTS: Twelve-hundred patients were included: 993 in the RP group and 207 in the IMRT group.The IMRT group had older age, PSA at diagnosis and a significantly higher percentage of cancer on the needle biopsy (p <0.001). Of the 207 patients who underwent IMRT, 54% presented comorbidities. Median follow-up was 91.7 months for the RP group and 76 months for the IMRT group. The OS at 5 and 7 was 96.2, and 93.7 for the RP group respectively and 88.4, and 83.1 for the IMRT group respectively (p <0.001). There were no significant differences in the CSS in relation to treatment received among the low- and high-risk groups, while in the intermediate-risk group, patients who underwent to RP had a higher CSS than patients who underwent IMRT (99.6% vs 94.1%, p=0.003). The IMRT group had a significantly better BDFS than the RP group (86.4% vs. 74.3%, respectively, p=0.016). CONCLUSIONS: Patients treated with RP were significantly younger and had a better prognosis than patients treated using IMRT, and according to our results, RP had better outcomes in terms of OS while IMRT had greater MOC. Treatment modality did not affect the CSS.

Comparison between measured and calculated dynamic wedge dose distributions using the anisotropic analytic algorithm and pencil-beam convolution.

We used the two available calculation algorithms of the Varian Eclipse 7.3 three-dimensional (3D) treatment planning system (TPS), the anisotropic analytic algorithm (AAA) and pencil-beam convolution (PBC), to compare measured and calculated two-dimensional enhanced dynamic wedge (2D EDW) dose distributions, plus implementation of the dynamic wedge into the TPS. Measurements were carried out for a 6-MV photon beam produced with a Clinac 2300C/D linear accelerator equipped with EDW, using ionization chambers for beam axis measurements and films for dose distributions. Using both algorithms, the calculations were performed by the TPS for symmetric square fields in a perpendicular configuration. Accuracy of the TPS was evaluated using a gamma index, allowing 3% dose variation and 3 mm distance to agreement (DTA) as the individual acceptance criteria. Beam axis wedge factors and percentage depth dose calculation were within 1% deviation between calculated and measured values. In the non-wedged direction, profiles exhibit variations lower than 2% of dose or 2 mm DTA. In the wedge direction, both algorithms reproduced the measured profiles within the acceptance criteria up to 30 degrees EDW. With larger wedge angles, the difference increased to 3%. The gamma distribution showed that, for field sizes of 10 x 10 cm or larger, using an EDW of 45 or 60 degrees, the field corners and the high-dose region of the distribution are not well modeled by PBC. For a 20 x 20 cm field, using a 60-degree EDW and PBC for calculation, the percentage of pixels that do not reach the acceptance criteria is 28.5%; but, using the AAA for the same conditions, this percentage is only 0.48% of the total distribution. Therefore, PBC is not reliable for planning a treatment when using a 60-degree EDW for large field sizes. In all the cases, AAA models wedged dose distributions more accurately than PBC did.

Commissioning and quality assurance for intensity modulated radiotherapy with dynamic multileaf collimator: experience of the Pontificia Universidad Católica de Chile.

The objective of this paper is to present our experience in the commissioning and quality assurance (QA) for intensity modulated radiotherapy (IMRT) using dynamic multileaf collimator (dMLC), sliding window technique. Using Varian equipment solution, the connectivity and operation between all IMRT chain components was checked. Then the following test were done: stability of leaf positioning and leaf speed, sensitivity to treatment interruptions (acceleration and deceleration), evaluation of standard field patterns, stability of dMLC output, segmental dose accuracy check, average leaf transmission, dosimetric leaf separation, effects of lateral disequilibrium between adjacent leaves in dose profiles and multiple carriage field verification. Standard patterns were generated for verification: uniform field, pyramid, hole, wedge, peaks and chair. Weekly QA Protocol include: sweeping gap output, Garden Fence Test (narrow bands, 2 mm wide, of exposure spaced at 2-cm intervals) and segmental dose accuracy check. Monthly QA include: sweeping gap output at multiple gantry and collimator angle, sweeping gap output off-axis, Picket Fence Test (eight consecutive movements of a 5-cm wide rectangular field spaced at 5-cm intervals), stability of leaf speed and leaf motor current test (PWM test). Patient QA procedure consists of an absolute dose measurement for all treatments fields in the treatment condition, analysis of actual leaf position versus planned leaf position (dynalog files) for each treatment field, film relative dose determination for each field, film relative dose determination for the plan (all treatment fields) in two axial planes and patient positioning verification with orthogonal films. The tests performed showed acceptable result. After more than one year of IMRT treatment the routine QA machine checks confirm the precision and stability of the IMRT system.

How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey.

BACKGROUND: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. METHODS: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. RESULTS: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. CONCLUSION: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC.

Calidad de vida a largo plazo en una cohorte de adultos mayores chilenos, tratados de cáncer de próstata con radioterapia de intensidad modulada (IMRT) / Long-term quality of life in a cohort of Chilean older adults, treated for Prostate cancer with modulated intensity radiotherapy (IMRT)

Introducción: El cáncer de próstata (CP) presenta una alta prevalencia. La radioterapia con intensidad modulada (IMRT) esuna nueva técnica con impacto poco conocido en la calidad de vida a largo plazo (CDVALP) de estos pacientes. El objetivo fue evaluar CDVALP en este grupo. Materiales y Método: Se incluyeron pacientes tratados entre 2000-2010, con más de 1 año de seguimiento. Se utilizó cuestionario EPIC, que fue completado directamente por el paciente. Se evaluaron dominios objetivos y subjetivos de hábitos urinarios, intestinales, hormonales y sexuales. Estudio aprobado por el comité de ética. Resultados: Se analizaron 45 encuestas. La mediana de edad fue 75 años (rango 55-90), seguimiento 4,4 años (rango 1,5-8,5). Tasa respuesta promedio fue de 96,9 por ciento. La toxicidad moderada-importante objetiva para dominio urinario fue: escape urinario 8,8 por ciento, disuria 4,4 por ciento, incontinencia 4,4 por ciento, uso pañales 2,2 por ciento, hematuria 6,6por ciento. En lo subjetivo, la polaquiuria fue "un problema grande" en 6,7 por ciento. La toxicidad intestinal objetiva moderada-importante fue: frecuencia deposición 8,9 por ciento, diarrea 4,4 por ciento, pujo 6,6 por ciento, incontinencia 4,4 por ciento, hematoquezia 0 por ciento. En el dominio hormonal: bochornos significativos 11,1 por ciento. En dominio sexual: compromiso importante del deseo 57,6 por ciento, erección 66,7 por ciento, orgasmo 55,6 por ciento, en globo 62,4 por ciento, Subjetivamente la disfunción eréctil se consideró "un problema grande" en 31,1 por ciento . En globo, la disfunción sexual subjetiva se consideró importante en 24,4 por ciento y moderada en 17,8 por ciento. Conclusiones: La radioterapia con IMRT se asocia a buena CDVALP en dominios urinario, intestinal, hormonal. La alta toxicidad sexual podría estar asociada a la edad avanzada de los pacientes tratados con radioterapia.(AU)

Background: Prostate cancer has a high prevalence. Intensity modulated radiation therapy (IMRT) is a new technique with little known impact on quality of life (QOL) in the long term of these patients. The objective was to evaluate QOL in this group. Materials and Methods: We included patients from 2000 to 2010, with more than 1 year follow-up. EPIC questionnaire was completed by the patient directly. We evaluated objective and subjective domains urinary and bowel habits, hormonal and sexual symptoms. Study approved by the ethics committee. Results: 45 surveys were analyzed. The median age was 75 years (range 55-90); follow up was 4.4 years (range 1.5-8.5). Average response rate was 96.9 percent. Toxicity moderately important objective for urinary domain was: urinary escape 8,8 percent, dysuria 4,4 percent, incontinence 4.4 percent, use diapers 2,2, hematuria 6,6 percent. In the subjective, polakiuria was "a big problem" in 6,7 percent. Objective Intestinal toxicity moderately important was: deposition rate 8,9. percent, diarrhea 4.4 percent, incontinence 4.4 percent, hematochezia 0 percent. In the hormonal domain clinical significant hot flashes in was 11.1 percent. In sexual domain: significant desire dysfunction in 57.6 percent, erection 66.7, orgasm 55.6 percent, Sexual overall 62.4 percent, subjectively erectile dysfunction was considered "a big problem" in 31.1 percent. Overall, subjective sexual dysfunction was considered important by 24.4 percent and moderate in 17.8 percent. Conclusions: IMRT radiation therapy is associated with good CDVALP in domains urinary, bowel, hormonal. The sexual high toxicity may be associated with older age of patients treated with radiotherapy.(AU)

Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis.

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.

[Postoperative radio-chemotherapy in locally advanced gastric cancer]. / Radio-quimioterapia postoperatoria en cáncer gástrico localmente avanzado.

BACKGROUND: Overall 5 years survival for surgically excised gastric cancer is 30%. Adjuvant treatment may improve the surgical results. AIM: To assess treatment results and toxicity in patients with surgically excised gastric cancer, treated with adjuvant radiotherapy and concomitant continuous 5-Fluorouracil (5-FU). MATERIAL AND METHODS: Forty one patients aged 32 to 73 years (29 males) with stage II-IVA gastric cancer, subjected to a total or subtotal gastrectomy and D2 nodal dissection between 1997 to 2006, were studied. They received adjuvant radiotherapy to the gastric bed and draining nodes in a total dose of 50.4 Gy in 28 fractions and chemotherapy with continuous infusion 5-FU, 200 mg/m(2)/day. Results were compared to historical controls matched according to demographic parameters and tumor characteristics. RESULTS: Eighteen patients were in stage II, 10 in stage IIIA, nine in stage IIIB and four in stage IVA. Twelve patients had an NO nodal status, 15 were NI, nine were N2 and five were N3. After a mean follow up of 32 months, 26 patients (63%) were alive. Five year overall survival was 49.6% for surgery plus radiochemotherapy compared to 30.7% for the historical group subjected only to surgery (p =0.002). Radiotherapy was associated with grade 1-2 toxicity and treatment was completed without interruptions in all patients. Chemotherapy was delayed temporarily in 3 patients. CONCLUSIONS: Adjuvant radio-chemotherapy improved overall survival in gastric cancer, compared to historical controls subjected only to surgical treatment.

Radio-quimioterapia postoperatoria en cáncer gástrico localmente avanzado / Postoperative radio-chemotherapy in locally advanced gastric cancer

Background: Overall 5 years survival for surgically excised gastric cancer is 30 percent. Adjuvant treatment may improve the surgical results. Aim: To assess treatment results and toxicity in patients with surgically excised gastric cancer, treated with adjuvant radiotherapy and concomitant continuous 5-Fluorouracil (5-FU). Material and Methods: Forty one patients aged 32 to 73 years (29 males) with stage II-IVA gastric cancer, subjected to a total or subtotal gastrectomy and D2 nodal dissection between 1997 to 2006, were studied. They received adjuvant radiotherapy to the gastric bed and draining lymphatic nodes in a total dose of 50.4 Gy in 28 fractions and chemotherapy with continuous infusión 5-FU, 200 mg/m²/day. Results were compared to historical controls matched according to demographic parameters and tumor characteristics. Results: Eighteen patients were in stage II, 10 in stage IIIA, nine in stage IIIB and four in stage IVA. Twelve patients had an NO nodal status, 15 were NI, nine were N2 and five were N3. After a mean follow up of 32 months, 26 patients (63 percent) were alive. Five year overall survival was 49.6 percent for surgery plus radiochemotherapy compared to 30.7 percent for the historical group subjected only to surgery (p =0.002). Radiotherapy was associated with grade 1-2 toxicity and treatment was completed without interruptions in all patients. Chemotherapy was delayed temporarily in 3 patients. Conclusions: Adjuvant radio-chemotherapy improved overall survival in gastric cancer, compared to historical controls subjected only to surgical treatment.