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.

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.

Exploring The Obesity Paradox In Atrial Fibrillation. AFBAR (Atrial Fibrillation Barbanza Area) Registry Results.

INTRODUCTION AND OBJECTIVES: Previous studies have described an inverse relationship between obesity and adverse events in a variety of conditions. Our aim was to investigate the relationship between obesity and prognosis in patients with atrial fibrillation. METHODS: We studied 746 patients who were prospectively included, between January and April 2008, in the AFBAR (Atrial Fibrillation in BARbanza area) registry. Patients were categorized into 3 body mass index groups using baseline measurements: normal (< 25 kg/m2), overweight (25-30 kg/m2), and obese (≥30 kg/m2). Survival free from the composite endpoint hospitalization for cardiovascular causes or all-cause mortality was compared across the 3 body mass index groups. A multivariable Cox proportional hazard regression was also performed to determine the independent effect of obesity as well as overweight, with respect to normal body mass index as a reference category, regarding the study endpoint. Median follow-up time was 36 (28-36) months. RESULTS: 49.3% were obese and 38.2% had overweight. The composite endpoint rate was 70.9%, 67.5%, and 57.6% for obese, overweight, and normal weight patients, respectively (log rank test; p=0.02). An inverse association of obesity with a favorable prognosis persisted even after multivariable adjustment: hazard ratio 0.668; 95% confidence interval 0.449-0.995; p=0.047. Hazard ratio of overweight, however, was 0.741; 95% confidence interval: 0.500-1.098; p=0.096. CONCLUSIONS: Obesity, defined as a body mass index ≥ 30 kg/m2, is associated with better prognosis in a community-based cohort of patients with atrial fibrillation.

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)

Comparison of unidimensional and bidimensional measurements in metastatic non-small cell lung cancer.

Tumour response evaluation after chemotherapy has become crucial in the development of many drugs. In contrast to the standard bidimensional WHO criteria, the recently described Response Evaluation Criteria In Solid Tumors are based on unidimensional measurements. The aim of the present study was to compare both methods in patients with metastatic non-small cell lung cancer. One hundred and sixty-four patients treated with two cisplatin-paclitaxel-based chemotherapy schedules between June 1994 and December 2000 were analysed. The measurements were reviewed by an independent panel of radiologists. Patient characteristics were: median age of 55 years (range 24-77 years) and a male to female ratio of 129 : 35. Adenocarcinoma and squamous carcinoma were the most common histologies. Vinorelbine was the third drug used in 77 patients and gemcitabine in 87. The ratio unidimensional/bidimensional was as follows: response 85 : 85; stable disease 32 : 32; progression 47 : 42 and not assessable 0 : 5. Kappa for agreement between responders was 0.951 (95% CI: 0.795-1.0) (P<0.001). Both WHO criteria and Response Evaluation Criteria In Solid Tumors give similar results in assessing tumour response in patients with non-small cell lung cancer after chemotherapy. The unidimensional measurement could replace the more complex bidimensional one.

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.

[Effect of PSA nadir and the time to nadir in the disease-free period in localized prostatic carcinoma treated with radical radiation]. / Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma prostático localizado tratado con irradiación radical.

OBJECTIVE: To evaluate the prognostic significance of PSA nadir (nPSA) and the time to nadir in disease free of recurrence (DFR) in localized carcinoma of prostate treated with radical radiotherapy (RTR). MATERIAL AND METHODS: From October 1984 to December 1998, 86 patients have been treated with prostate carcinoma. It was considered of Low risk those patients with PSA < or = 10 ng/ml, Gleason = 6 or stage T1-T2. Moderate risk: those with one elevated of the three parameters. High risk: two or more parameters. The treatment was carried out in a lineal accelerator using photons of 15 MV, with standard technique and frationation, administering a median dose of 66 Gy (58-75 Gy). It was defined disease free of recurrence (DFR), the time to clinical PSA or biochemical failure. This one was defined as the time starting from the date of nadir PSA to the second consecutive increase of PSA value after three separate serial measurements separated for at least one month. RESULTS: The median of initial PSA value was of 16 ng/ml (1-270), initial clinical stage T1-T2 (70p), stages T3-T4 (14p), and unknown in 2p. The median of Gleason score was 6 (2-10). According to the group of risk they were classified as: low risk in 16 patients (19%), moderated risk in 22 patients (26%), high risk in 21 patients (24%), and unknown in 27 patients (31%). Median nPSA value was 0.8 ng/ml (limits: 0-139) and the median time elapsed between the initial PSA and nPSA has been of 11 months (limits: 0-72 months). The actuarial DFR projected to five years in those patients with nPSA = 1 ng/ml was of 67% vs. 47% in patient with nPSA figures > 1 ng/ml (p = 0.0018). The PFD in patients with time to nadir (t nadir) < 12 months it was of 20% vs. 80% in patients with t nadir > 12 months (p < 0.0001). Multivariate analysis demonstrated that time to nadir (H.R: 0.11 p = 0.001), group of risk (H.R: 28.72 p = 0.020), and grade of differentiation (HR: 28.72 p = 0.010), were determinant to DFR. CONCLUSIONS: nPSA is an important factor to determine the objective response to radiotherapy. nPSA and time to nadir are prognostic factors that influences significantly on the DFR. The indication of adjuvant treatment in those patients with unfavorable prognostic factors such us those who do not reach nadir PSA < or = 1 ng/ml and time to nadir < or = 12 months, deserves the realization of a prospective study.

Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (pie) del carcinoma prostatico localizado tratado con irradiación radical / Prognostic significance of PSA nadir and the time to nadir in disease free of recurrence in localized carcinoma of prostate treated with radical radiotherapy

Objetivo: Valorar el significado pronóstico del nadir de PSA (nPSA) y del tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma de próstata localizado tratado con radioterapia radical (RTR). Material y métodos: Desde Octubre 1984 hasta Diciembre 1998 se han tratado 86 (p) con el diagnóstico de carcinoma de próstata. Se consideró de Bajo riesgo aquellos pacientes con PSA 1 ng/ml (p= 0,0018). El PLE a 5 años en pacientes con tiempo a nadir (t nadir) 12 meses (p<0,0001). El estudio multivariado demostró diferencias estadísticamente significativas para factores como tiempo t nadir (H.R: 0,11 p=0,001), grupos de riesgo (H.R: 28,72 p=0,020), y grado de diferenciación (HR: 28,72 p=0,010).Conclusiones: El nPSA es un factor importante para determinar la respuesta objetiva a la RT. El nPSA y t nadir son factores pronósticos que influyen significativamente sobre el PLE. La indicación de un tratamiento complementario en aquellos pacientes con factores pronósticos desfavorables como en el grupo que no llega a un nadir<= 1 ng/ml y en aquellos con tnadir menor de doce meses, merece la realización de un estudio prospectivo (AU)