Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision.

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis

Background Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. Methods A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984–2000) at a median dose of 15 Gy (range 10–20 Gy) and 25 patients received adjuvant PHDRB (2001–2016) at a median dose of 32 Gy (range 24–40 Gy) in 6, 8, or 10 b.i.d. fractions. Results The median follow-up was 5.6 years (range 0.5–14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. Conclusions IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain (AU)

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.

Stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer

Purpose: To investigate whether bone metastases-directed stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer (OPC). Methods and material: OPC is usually managed with androgen deprivation therapy (ADT). Migration to castration-resistant prostate cancer will inevitably occur in the majority of these patients. There are several strategies aimed to delay the emergence of castration resistance including intermittent ADT, second generation antiandrogens (abiraterone, enzalutamide) or metastases-directed SBRT. The present report describes two cases of patients with OPC that received SBRT 24 Gy/3Rx to the solitary bony lesion after ADT failure. Results: Both cases showed complete and durable biochemical response for 13 and 17 months, respectively. Conclusions: SBRT can be used to delay the emergence of castration resistance and the need for systemic therapy when used after ADT failure (AU)

No disponible

Stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer.

PURPOSE: To investigate whether bon e metastases-directed stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer (OPC). METHODS AND MATERIAL: OPC is usually managed with androgen deprivation therapy (ADT). Migration to castration-resistant prostate cancer will inevitably occur in the majority of these patients. There are several strategies aimed to delay the emergence of castration resistance including intermittent ADT, second generation antiandrogens (abiraterone, enzalutamide) or metastases-directed SBRT. The present report describes two cases of patients with OPC that received SBRT 24 Gy/3Rx to the solitary bony lesion after ADT failure. RESULTS: Both cases showed complete and durable biochemical response for 13 and 17 months, respectively. CONCLUSIONS: SBRT can be used to delay the emergence of castration resistance and the need for systemic therapy when used after ADT failure.

Intraoperative radiotherapy-containing multidisciplinary management of trunk-wall soft-tissue sarcomas

PURPOSE: A joint analysis of data from centers within the intraoperative radiotherapy (IORT)-Spanish cooperative initiative was performed to investigate the main contributions of IORT to the multidisciplinary treatment of trunk-wall soft-tissue sarcoma (TW-STS). MATERIALS AND METHODS: Patients with a histologic diagnosis of TW-STS (primary tumor 53 %; locally recurrent 47 %) with absence of distant metastases, undergoing surgery with radical intent and IORT (median dose 12.5 Gy) were considered eligible for participation in this study. In addition, all primary tumors received external-beam radiotherapy (median dose 50 Gy). RESULTS: From 1986 to 2012, a total of 68 patients were analyzed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316), 5-year local control (LC) was 58 %. Five-year IORT in-field control, disease-free survival (DFS) and overall survival were 70, 45 and 51 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 3.97, p < 0.001). In regard to IORT in field control, incomplete resection (HR 3.23, p = 0.008) and recurrent disease status (HR 2.52, p = 0.04) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that margin and disease status influences local and central control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy (AU)

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Intraoperative radiotherapy-containing multidisciplinary management of trunk-wall soft-tissue sarcomas.

PURPOSE: A joint analysis of data from centers within the intraoperative radiotherapy (IORT)-Spanish cooperative initiative was performed to investigate the main contributions of IORT to the multidisciplinary treatment of trunk-wall soft-tissue sarcoma (TW-STS). MATERIALS AND METHODS: Patients with a histologic diagnosis of TW-STS (primary tumor 53 %; locally recurrent 47 %) with absence of distant metastases, undergoing surgery with radical intent and IORT (median dose 12.5 Gy) were considered eligible for participation in this study. In addition, all primary tumors received external-beam radiotherapy (median dose 50 Gy). RESULTS: From 1986 to 2012, a total of 68 patients were analyzed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316), 5-year local control (LC) was 58 %. Five-year IORT in-field control, disease-free survival (DFS) and overall survival were 70, 45 and 51 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 3.97, p < 0.001). In regard to IORT in field control, incomplete resection (HR 3.23, p = 0.008) and recurrent disease status (HR 2.52, p = 0.04) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that margin and disease status influences local and central control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.

[Radiotherapy in breast cancer: standards and new directions, accelerated partial breast irradiation]. / Tratamiento radioterápico del cáncer mama: estándares y nuevas tendencias. Irradiación parcial acelerada de la mama.

Radiotherapy as a part of the breast cancer treatment has evolved in the last decades. Post-mastectomy radiotherapy produces a substantial reduction in the risk of local recurrence as well as a moderate, but definitive reduction in long-term breast cancer mortality in women at high risk of locoregional failure. Whole-breast irradiation, as part of breast-conservation therapy, has well-established results with good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This has led investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) is a collection of radiotherapy techniques that deliver higher daily doses of radiation to the surgical cavity with margin over a shorter time than whole breast irradiation (from 6-6.5 weeks to 1 week). Early results of this approach have demonstrated excellent local control, minimal acute toxicity, and are more convenient for the patient. Phase III randomized clinical trials are currently underway to assess local control, acute and chronic toxicities. APBI extend the choise of breast conservation.

Tratamiento radioterápico del cáncer mama: estándares y nuevas tendencias. Irradiación parcial acelerada de la mama / No disponible

La radioterapia (RT) como parte del tratamiento del cáncer de mamaha evolucionado mucho en las últimas décadas.La radioterapia post-mastectomía (RTPM) aporta una reducción sustancialdel riesgo de recurrencia local así como una moderada, perodefi nitiva, reducción en la mortalidad a largo plazo en mujeres con altoriesgo de recurrencia locorregional.La irradiación de todo el volumen mamario, como parte del tratamientoconservador de la mama, consigue buenos resultados en cuanto a controlde la enfermedad, cosmesis, y toxicidad. Los resultados de grandesensayos clínicos sugieren que el riesgo de recurrencia local ipsilateralreside fundamentalmente en las inmediaciones del lecho tumoral.Esto, ha llevado a los investigadores a buscar un tipo de radiación másacelerada y más dirigida sobre el lecho tumoral. La irradiación parcialacelerada de la mama (APBI), puede llevarse a cabo mediante distintastécnicas que administran dosis de radiación más altas sobre la cavidadquirúrgica con un margen de seguridad, en un tiempo más reducidoque la irradiación de toda la mama (de 6-6,5 semanas a 1 semana).Los resultados a corto plazo de esta aproximación terapéutica handemostrado excelente control local, mínimos efectos adversos agudosy una mayor comodidad para las pacientes.Se están llevando a cabo ensayos fases III aleatorizados para confi rmarla equivalencia de la APBI con la irradiación de toda la mama. La confirmación de estos resultados permitirá a un mayor número de pacientesoptar por un tratamiento conservador de la mama(AU)

Radiotherapy as a part of the breast cancer treatment has evolved inthe last decades. Post-mastectomy radiotherapy produces a substantialreduction in the risk of local recurrence as well as a moderate, but definitive reduction in long-term breast cancer mortality in women at highrisk of locoregional failure.Whole-breast irradiation, as part of breast-conservation therapy, haswell-established results with good cosmesis, and low toxicity. Resultsfrom the BCT trials suggest that the risk for ipsilateral breast cancerrecurrence resides within close proximity to the original tumor site. Thishas led investigators to consider the role of an accelerated and moretumor bed-focused course of radiotherapy. Accelerated partial-breastirradiation (APBI) is a collection of radiotherapy techniques that deliverhigher daily doses of radiation to the surgical cavity with margin overa shorter time than whole breast irradiation (from 6-6.5 weeks to 1week). Early results of this approach have demonstrated excellent localcontrol, minimal acute toxicity, and are more convenient for the patient.Phase III randomized clinical trials are currently underway to assesslocal control, acute and chronic toxicities. APBI extend the choise ofbreast conservation(AU)

Tratamiento radioterápico del cáncer mama: estándares ynuevas tendencias. Irradiación parcial acelerada de la mama / Radiotherapy in breast cancer: standards and new directions, accelerated partial

La radioterapia (RT) como parte del tratamiento del cáncer de mamaha evolucionado mucho en las últimas décadas.La radioterapia post-mastectomía (RTPM) aporta una reducción sustancialdel riesgo de recurrencia local así como una moderada, perodefi nitiva, reducción en la mortalidad a largo plazo en mujeres con altoriesgo de recurrencia locorregional.La irradiación de todo el volumen mamario, como parte del tratamientoconservador de la mama, consigue buenos resultados en cuanto a controlde la enfermedad, cosmesis, y toxicidad. Los resultados de grandesensayos clínicos sugieren que el riesgo de recurrencia local ipsilateralreside fundamentalmente en las inmediaciones del lecho tumoral.Esto, ha llevado a los investigadores a buscar un tipo de radiación másacelerada y más dirigida sobre el lecho tumoral. La irradiación parcialacelerada de la mama (APBI), puede llevarse a cabo mediante distintastécnicas que administran dosis de radiación más altas sobre la cavidadquirúrgica con un margen de seguridad, en un tiempo más reducidoque la irradiación de toda la mama (de 6-6,5 semanas a 1 semana).Los resultados a corto plazo de esta aproximación terapéutica handemostrado excelente control local, mínimos efectos adversos agudosy una mayor comodidad para las pacientes.Se están llevando a cabo ensayos fases III aleatorizados para confi rmarla equivalencia de la APBI con la irradiación de toda la mama. La confirmación de estos resultados permitirá a un mayor número de pacientesoptar por un tratamiento conservador de la mama (AU)

Radiotherapy as a part of the breast cancer treatment has evolved inthe last decades. Post-mastectomy radiotherapy produces a substantialreduction in the risk of local recurrence as well as a moderate, but definitive reduction in long-term breast cancer mortality in women at highrisk of locoregional failure.Whole-breast irradiation, as part of breast-conservation therapy, haswell-established results with good cosmesis, and low toxicity. Resultsfrom the BCT trials suggest that the risk for ipsilateral breast cancerrecurrence resides within close proximity to the original tumor site. Thishas led investigators to consider the role of an accelerated and moretumor bed-focused course of radiotherapy. Accelerated partial-breastirradiation (APBI) is a collection of radiotherapy techniques that deliverhigher daily doses of radiation to the surgical cavity with margin overa shorter time than whole breast irradiation (from 6-6.5 weeks to 1week). Early results of this approach have demonstrated excellent localcontrol, minimal acute toxicity, and are more convenient for the patient.Phase III randomized clinical trials are currently underway to assesslocal control, acute and chronic toxicities. APBI extend the choise ofbreast conservation (AU)

Sarcoma de partes blandas: ¿existe posibilidad de rescate cuando la primera cirugía no fue resolutiva? / Soft tissue sarcoma: can a rescue procedure be performed when the first surgery was unsuccessful?

Objetivo. El objetivo de este trabajo es revisar la experiencia de nuestro centro en el tratamiento de pacientes diagnosticados de sarcoma de partes blandas (SPB) en una extremidad que consultan tras resecciones quirúrgicas inadecuadas o recidiva local. Material y método. Se trata de un estudio retrospectivo de 64 pacientes remitidos tras el tratamiento de un SPB en otro centro, divididos en 2 grupos: el grupo A, compuesto por 27 pacientes a quienes se realizó una escisión inadecuada inicial (whoops procedure) y el grupo B, con 37 pacientes afectos de una recidiva local de un SPB. Se calculó la tasa de supervivencia libre de enfermedad y la tasa de supervivencia acumulada (Kaplan-Meier). Resultados. Grupo A: la totalidad de los 27 pacientes fueron reintervenidos y en 12 casos se detectó enfermedad tumoral residual (un 44%). Veintitrés pacientes recibieron radioterapia asociada (intraoperatoria, braquiterapia y/o externa). El seguimiento medio ha sido de 67 meses (24-216) Tres pacientes presentaron recidiva local, uno de los cuales precisó amputación. El 11% de los pacientes habían fallecido en el momento de la revisión. La tasa de supervivencia libre de enfermedad a los 216 meses ha sido del 85%. Grupo B: 35 de los 37 pacientes fueron reintervenidos (94%). En 21 casos se asoció quimioterapia y en 4 perfusión aislada de la extremidad con factor de necrosis tumoral (TNF) y melfalan (10,8%). Veintisiete pacientes recibieron radioterapia (externa, intraoperatoria y/o braquiterapia) (72%), 19 de ellos habían recibido ya radioterapia después de la primera (70%). En 20 casos (10%) se asoció quimio-terapia y radioterapia. La media de seguimiento ha sido de 80 meses (12-264). Dieciséis pacientes presentaron metástasis después del tratamiento y diecinueve tuvieron complicaciones mayores. El 43% de los pacientes había fallecido en el momento de la revisión. La tasa de supervivencia libre de enfermedad a los 264 meses ha sido del 16%. Conclusiones. Después de una escisión inadecuada inicial se puede obtener una alta tasa de supervivencia libre de enfermedad en pacientes remitidos inmediatamente a centros especializados. Sin embargo, cuando aparece la recidiva local, las posibilidades de supervivencia libre de enfermedad disminuyen drásticamente

Purpose. The purpose of this paper is to review the experience of our hospital in treating patients diagnosed with a soft-tissue sarcoma (STS) in one of their limbs who sought consultation further to inappropriate surgical resections or a local relapse. Materials and methods. This is a retrospective study of 64 patients treated for STS in another hospital; the patients were divided into 2 groups: group A, comprised 27 patients where the initial excision proved to be inappropriate («whoops procedure»); group B was made up of 37 patients that had a local recurrence of a STS. The disease-free and accumulated (Kaplan-Meier) survivorship rates were calculated. Results. Group A: all 27 patients were reoperated and in 12 cases a residual tumoral disease was detected (44%). Twenty-three patients received associated radiotherapy (intraoperatively, brachytherapy and/or external beam radiotherapy). Mean follow up was 67 months (24-216) Three had a local recurrence, two of them requiring amputation. Eleven percent of patients had died at the time of examination. The disease-free survivorship rate at 216 months was 85%. Group B: 35 of the 37 patients were reoperated (94%). Chemotherapy was used in 21 cases and in four cases isolated limb perfusion was used with TNF and melphalan (10.8%). Twenty-seven patients received radiotherapy (external beam, intraoperative and/or brachytherapy) (72%), 19 of them had received radiotherapy after the first one (70%). In 20 cases (10%) both chemotherapy and radiotherapy were used. Mean follow-up was 80 months (range: 12-264). Sixteen patients had metastasis further to treatment and nineteen had major complications. Forty-three percent of patients had died at the time of this review. Disease-free survivorship at 264 months was 16%. Conclusions. After a «whoops procedure» it is possible to obtain a high disease-free survivorship rate in patients referred immediately to specialized units. Nevertheless, when local recurrence occurs, the disease-free survivorship rate decreases sharply

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP (AU)

Fixed higher dose schedule of suramin plus hydrocortisone in patients with hormone refractory prostate carcinoma a multicenter Phase II study.

BACKGROUND: Using a fixed higher-dose schedule, the efficacy and toxicity of suramin plus hydrocortisone were assessed in patients with metastatic hormone-refractory prostate carcinoma (HRPC). METHODS: Fifty consecutive patients with HRPC (including those in whom hormonotherapy was withdrawn) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited. Treatment was comprised of a bolus intravenous infusion of 200 mg of suramin followed by suramin (500 mg/m(2) intravenously [i.v.] over 24 hours) given daily over 5 days as a loading course, followed by suramin (350 mg/m(2) i.v. over 2 hours) administered weekly for 12 weeks. This 12-week course was repeated at 6-month intervals. All patients received concomitant hydrocortisone. RESULTS: Five hundred fifty weekly doses of therapy were delivered over the course of the entire study. A partial response, based on a > 50% decrease in the prostate specific antigen (PSA) level, was achieved in 27 patients (54%; 95% confidence interval [95% CI], 44.7-65.0%), 16 of whom (32%; 95%CI, 23.9-43.2%) had a > 75% decrease in their PSA levels. The measurable disease objective response rate was 18% (95% CI, 2.3-51.8%). Of the 37 patients with bone pain requiring analgesia, 27 patients (73%; 95% CI, 55.9-86.2%) reduced their medication consumption to a lower level on the World Health Organization analgesic ladder. The median duration of response was 15.5 weeks (range, 6-70 weeks), the median time to disease progression was 13 weeks, and the median overall survival time was 11 months. Treatment generally was well tolerated. Fatigue and severe lymphopenia were the most commonly reported significant toxicities. In addition, there was 1 septic toxic death reported, and 10% of the patients were found to have NCI Grade 3-4 neurotoxicity. CONCLUSIONS: The results of the current study demonstrated that the fixed-dose suramin regimen administered herein showed high, although short-lived, activity and a good tolerance profile in HRPC patients.

Papel y eficacia de la radioterapia intraoperatoria en el tratamiento adyuvante tras rescate quirúrgico de la recidiva del cáncer de cérvix / Role and efficacy of intraoperative radiotherapy in adjuvant therapy after rescue surgery for cervical cancer recurrence

Objetivo: Determinar la toxicidad y la utilidad clínica de la radioterapia intraoperatoria con electrones (RIO) en pacientes con recurrencia de cáncer de cérvix.Material y métodos: Entre enero de 1986 y junio de 1999, se trataron 36 pacientes con RIO. Las pacientes con recurrencia tras cirugía exclusiva recibieron quimiorradioterapia preoperatoria con 20 mg/m2 de cisplatino y 1.000 mg/m2 de 5fluorouracilo, un ciclo al iniciar y otro al acabar la radioterapia externa (45 Gy). Las pacientes con recurrencia tras radioterapia fueron evaluadas para cirugía como primera opción. La dosis media de RIO fue de 15 Gy (límites 10-20).Resultados: La tasa global de toxicidad atribuible a la RIO fue del 17 por ciento, a expensas de dolor crónico en 6 pacientes. La tasa de control a 10 años en el área tratada con RIO fue del 56 por ciento. El control se correlacionó con la afectación del margen parametrial (p = 0,001), la cantidad de enfermedad residual (p = 0,001) y la afectación de ganglios pélvicos (p = 0,032).Conclusiones: La RIO es una técnica útil en el manejo de la recurrencia del cáncer de cérvix resecable. Las pacientes con afectación de ganglios linfáticos pélvicos, afección parametrial, y/o exéresis incompleta tienen un control local muy pobre a pesar de la RIO a las dosis empleadas en este estudio. (AU)

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

Intraoperative electron beam radiotherapy during radical surgery for locally advanced and recurrent cervical cancer.

OBJECTIVE: The goal of this study was to determine the toxicity patterns and clinical usefulness of intraoperative electron beam radiotherapy (IOERT) in patients with unfavorable-outcome cervical cancer. METHODS: From January 1986 to June 1999, 67 patients (36 recurrent, 31 primary disease) were treated with IOERT. Previously unirradiated patients received preoperative chemoradiation to 45 Gy with cisplatin 20 mg/m(2) and 5-fluorouracil 1000 mg/m(2). IOERT median dose was 12 Gy for primary disease (range: 10-25) and 15 Gy for recurrent disease (range: 10-20). RESULTS: The 10-year control rate within the area treated with IOERT ("in-field" (IF)) for the entire group was 69.4, with 92.8 and 46.4% 10-year IF control rates for the primary and recurrent patients, respectively. IF control rate correlated with involvement of the parametrial margin (P = 0.001), amount of residual disease (P = 0.001), and pelvic lymph node involvement (P = 0.032). The overall incidence of toxic events that might be attributable to IOERT was 14.9%. Chronic pain was observed in 8 of 67 evaluable patients (11.9%) and motor neuropathy of the lower extremity in one patient (3.2%). CONCLUSIONS: IOERT is a valuable boosting technique in the management of advanced but resectable cervical cancer. Patients, especially recurrent cases, with positive lymph nodes, parametrial involvement, and/or incomplete resections have poor local control rates despite IOERT at the doses used in this study.

Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer.

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)-based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU-based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P =.036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P =.17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU-based chemoradiation.