Later outcomes and alpha/beta estimate from hypofractionated conformal three-dimensional radiotherapy versus standard fractionation for localized prostate cancer.

PURPOSE: Now that the follow-up time has exceeded 5 years, an estimate of the α/ß ratio can be presented. The additional late outcomes in patients treated with three-dimensional conformal external beam radiotherapy for localized prostate cancer using a hypofractionated vs. a standard fractionation regimen are reported from this prospective nonrandomized contemporary comparison. METHODS AND MATERIALS: A total of 114 nonrandomized patients chose hypofractionation delivered in 20 fractions of 3 Gy or 3.15 Gy (mean 3.06 Gy) for localized prostate cancer within a median overall time of 32 days (range, 29-49) using four fractions weekly. A total of 160 comparable patients were contemporarily treated within a median of 55 days (range 49-66). The median follow-up was 66 months (range, 24-95) for the hypofractionated arm and 63 months (range, 36-92) for the standard arm. The percentage of patients in the low-, medium-, and high-risk groups was 36%, 46%, and 18% in the hypofractionated arm and 44%, 50%, and 6% in standard arm (2 Gy), respectively. RESULTS: The 5-year actuarial biochemical absence of disease (prostate-specific antigen nadir + 2 ng/mL) and disease-free survival rate was the same at 89% in both arms, making the α/ß calculation unambiguous. The point ratio of α/ß was 1.86 (95% confidence interval, 0.7-5.1 Gy). The 95% confidence interval was determined entirely by the binomial confidence limits in the numbers of patients. Rectal reactions of grade 3 and 4 occurred in 1 of 114 (hypofractionated) and 2 of 160 (standard) patients. CONCLUSIONS: The presented three-dimensional conformal regimen was acceptable, and the α/ß value was 1.8, in agreement with other very recent low meta-analyses (reviewed in the "Discussion" section).

Late outcomes following hypofractionated conformal radiotherapy vs. standard fractionation for localized prostate cancer: a nonrandomized contemporary comparison.

PURPOSE: To study retrospectively late complications and biochemical control in patients treated with three-dimensional conformal external-beam radiotherapy for localized prostate cancer administered using hypofractionation vs. a standard fractionation regimen. The hypofractionation regimen (Hypo) was designed to avoid more late rectal reactions and to be done in half as many treatment sessions. METHODS AND MATERIALS: Eighty-nine nonrandomized patients chose Hypo delivered in 20 fractions of 3 Gy (n = 52) or 3.15 Gy (n = 37) for a median overall treatment time of 33 days. One hundred thirty comparable patients were contemporaneously treated with standard fractionation to a median dose of 78 Gy delivered over 55 days. The median follow-up time was 49 months (range, 24-73 months). RESULTS: The 5-year actuarial biochemical control rates were 96%, 84%, and 85% for low-, medium-, and high-risk disease in the Hypo group, respectively. The respective rates in the standard fractionation group were 98%, 84%, and 87%, with no statistical difference between the two groups. The rate of rectal Grade 2-4 complications was 5.5% in both treatment groups and of urinary Grade 2-4 complications was 5.6% in the Hypo and 3% in the standard group (p = 0.36). Similarly, there were no statistical differences in the rate of late complications between patients treated with 3 Gy/fraction vs. 3.15 Gy/fraction. CONCLUSIONS: Our preliminary results showed that the Hypo regimen is feasible and does not reduce biochemical control compared with standard fractionation. The incidence of late complications was not increased when the tumor normalized total doses at 2Gy/fraction was increased from 77.1 to 83.7 Gy in patients treated with either 3 or 3.15 Gy/fraction in the Hypo group, respectively.

Acute toxicity after hypofractionated conformal radiotherapy for localized prostate cancer: nonrandomized contemporary comparison with standard fractionation.

PURPOSE: To prospectively study acute rectal and urinary reactions from three-dimensional conformal external beam radiotherapy for localized prostate cancer comparing two hypofractionation regimens with standard fractionation (standard). The hypofractionation regimens were designed to avoid more late reactions in the hypofractionation groups than in the standard group, with the advantage of one-half as many treatment sessions. PATIENTS AND MATERIALS: A total of 56 nonrandomized patients chose hypofractionation delivered at 3 (n = 22) or 3.15 (n = 34) Gy/fraction, 4 d/wk, to a total dose of 60 or 63 Gy within 5 weeks. A total of 74 patients were contemporarily treated with standard fractionation at 2 Gy/fraction, 5 d/wk, to a total dose of 76 to 80 Gy. RESULTS: The differences within patients without complications were not statistically significant in the three groups. However, for acute complications of Grade 2 or worse, the Hypo3.15 group had significantly greater (p = 0.001) complication rates (50%) compared with the standard group (17%). The incidence of patients without acute rectal complications was significantly lower for the Hypo3.15 group compared with the Hypo3 and standard groups. The incidence of rectal Grade 2 or greater complications was correspondingly significantly greater for the Hypo3.15 group than for the Hypo3 and standard groups (p < 0.001). The incidence of patients with urinary complications was not significantly different among the three groups. CONCLUSIONS: Acute rectal reactions were more frequent and intense in the Hypo3.15 group than in the Hypo3 and standard groups. In our study, 60 Gy at 3 Gy/fraction within 5 weeks resulted in acute toxicity similar to that after standard fractionation.

Factores pronósticos en radioterapiadel cáncer de próstata. Importancia dela dosis y de la hormonoterapia de inducción / Prognosis in prostate cancer radiotherapy. Importance of dosage and inductive hormonetherapy

Introducción: se estudiaron los efectos de la dosis de radioterapia y del uso de hormonoterapia asociada en pacientes con cáncer de próstata, sobre la sobrevida libre de recaída bioquímica, lamortalidad causa específica y la mortalidad global. Material y método: se analizaron 910 pacientes consecutivos tratados radicalmente con radioterapiaconformada tridimensional entre 1993 y 2005. Resultados: para pacientes que recibieron una dosis mediana de 74 Gy el control bioquímico actuarial a diez años fue 78%, 60% y 40% para los grupos de riesgo bajo, intermedio y alto,respectivamente. Para pacientes con una dosis mediana de 78 Gy, el control bioquímico fue 96%, 81% y 40% para los mismos grupos, respectivamente. La diferencia entre los grupos de riesgo bajo e intermedio fue p = 0,029 y 0,008, respectivamente. El análisis multivariado confirmó que elescalamiento de dosis correlacionó significativamente con el control bioquímico y con la sobrevidacausa específica. Asimismo, la hormonoterapia fue significativa para el control bioquímico y la sobrevida causa específica. La tasa actuarial de complicaciones tardías grados 2 y 3 a diez años (no hubo complicaciones grados 4 y 5) no fue significativamente diferente entre cuatro grupos de dosisdistribuidos entre 64 Gy y 80 Gy. Para pacientes tratados con dosis entre 78 Gy y 80 Gy las complicaciones tardías urinarias fueron 4,8% y las rectales 5,3%. La hormonoterapia no aumentó latasa de complicaciones tardías. En pacientes sin hormonoterapia asociada a la radioterapia, un nadir <1 ng/ml y su manifestación más de 12 meses después del tratamiento estuvo con control bioquímico. Conclusiones: la administración de dosis de radioterapia conformada tridimensional entre 77 Gy y 80 Gy y el uso de hormonoterapia de inducción han permitido mejorar los resultados de control bioquímico y sobrevida causa específica en todos los grupos de riesgo. Esta mejoría no se ha acompañado de un aumento de la tasa de complicaciones tardías.

Introduction: we aimed to analyse the effects of radiotherapy dose and the use of neoadjuvant hormone therapyon survival without biochemical relapse, on specific cause mortality and on overall mortality, in patients with prostate cancer.Methods: we analysed 910 consecutive patients treated with radical tridimensional conformal radiotherapybetween 1993 and 2005.Results: actuarial biochemical control at 10 years for the subset of patients who received a median dose of 74 Gy was 78%, 60% and 40% for the low, medium and highrisk groups, respectively. Biochemical control of patients receiving a median dose of 78 Gy was 96%, 81% and 40% for the same risk-groups. The difference between low and medium risk groups was p=0,029 y 0,008, respectively.Mulitvariate analysis confirmed that dose escalation significantlycorrelated with biochemical control and causespecific survival. Likewise, hormone therapy was a significantfactor for biochemical control and cause-specific survival. The 10-year actuarial rate of Grade 2 and Grade 3 late complications (there were no Grade 4 or 5 complications) presented non-significant differences between foursubsets of patients treated with doses from 64 to 80 Gy. 4.8% of patients treated with doses between 78 and 80 Gy presented late urinary complications, and 5.3% of them showed late rectal complications. In hormone therapy naïvepatients a <1 ng/ml nadir and its manifestation more than12 months after finishing treatment, significantly correlated with biochemical control.Conclusions: administration of a dose between 77 and 80 Gy with external beam 3D conformal radiotherapy, together with the use of induction hormone therapy have improved biochemical control results and cause-specific survival in all risk groups. No increase of late complications was observed.

Introdução: os efeitos da dose de radioterapia e de sua associação com hormonoterapia sobre a sobrevida semrecaída bioquímica, a mortalidade por causa específica e a mortalidade global foram estudados em pacientes comcâncer de próstata Material e método: foram analisados 910 pacientesconsecutivos tratados radicalmente com radioterapia conformadatridimensional entre 1993 e 2005.Resultados: nos pacientes que receberam uma dose média de 74 Gy o controle bioquímico atuarial aos dezanos foi 78%, 60% e 40% para os grupos com risco baixo, médio e alto respectivamente. Nos pacientes com dose média de 78 Gy, o controle bioquímico foi 96%, 81% e 40%para os mesmos grupos, respectivamente. A diferença entreos grupos de riscos baixo e médio foi de p = 0,029 e 0,008, respectivamente. A análise multivariada confirmou que oaumento progressivo da dose teve uma correlação significativa com o controle bioquímico e com a sobrevida porcausa específica. A hormonoterapia foi significativa para o controle bioquímico e a sobrevida por causa específica.A taxa atuarial de complicações tardias de segundo e terceiro graus a dez anos (não houve complicações de quarto e quinto graus) não foi significativamente diferente nos quatro grupos com doses entre 64 Gy e 80 Gy. As complicações tardias urinarias foram de 4,8% e as retais de 5,3% nos pacientes tratados com doses entre 78 Gy e 80 Gy. A hormonoterapia não aumentou a taxa de complica ções tardias. Em pacientes sem hormonoterapia associada à radioterapia, um nadir <1 ng/ml e suamanifestação depois de 12 meses do tratamento estava relacionada significativamente com o controle bioquímico. Conclusões: a administração de doses de radioterapia conformada tridimensional entre 77 Gy e 80 Gy e o uso de hormonoterapia de indução levaram a uma melhora dos resultados de controle bioquímico e sobrevida por causa específica em todos os grupos de risco. Esta melhora não foi acompanhada por um aumento da taxa de complicações tardias.

Irradiación posprostatectomía radical. Confirmación de resultados preliminares previos / Radical postprostatectomy irradiation: preliminary results

Introducción: se estudiaron los resultados de la irradiación posprostatectomía radical por cáncer de próstata. Material y método: se analizaron 131 pacientes consecutivos tratados entre 1994 y 2004. Treinta y ocho pacientes fueron irradiados en forma adyuvante por presentar factores de riesgo elevado de recidiva local posoperatoria, y 93 por recaídas bioquímicas luego de la cirugía (59 de ellos presentaban una recidiva palpable en la pelvis). Resultados: la sobrevida actuarial libre de recaída bioquímica, la sobrevida causa específica y la sobrevida global a los cinco años luego de la irradiación fueron 90 por ciento, 100 por ciento y 97 por ciento para los pacientes tratados con radioterapia adyuvante, y 65 por ciento, 95 por ciento y 90 por ciento para los pacientes tratados con radioterapia de rescate, respectivamente. En estos últimos, cuando no se hubiere empleado hormonoterapia asociada, la comprobación de descenso del nivel de antígeno prostático específico (PSA) a los 50 Gy orienta hacia un mejor control bioquímico. Las complicaciones tardías urinarias fueron más frecuentes que cuando se empleó solamente la radioterapia como tratamiento radical de inicio. Conclusiones: los resultados obtenidos confirman las tendencias observadas en una publicación preliminar previa sobre los beneficios de la radioterapia posprostatectomía.

Irradiación posprostatectomía del cancer de próstata: un an lisis preliminar / Prostatectomy of prostate cancer: a preliminary analysis

Se estudiaron los resultados de la irradiación posprostatectomía radical por c ncer de próstata. Se analizaron 62 pacientes consecutivos tratados entre 1994 y 2002. Veinte pacientes fueron irradiados en forma adyuvante por presentar factores de riesgo elevado de recidiva local posoperatoria, y 42 por recaídas bioquímicas luego de la cirugía (17 de ellos presentaban una recidiva palpable en la pelvis). La sobrevida actuarial libre de recaída bioquímica, la sobrevida causa específica y la sobrevida global a los cinco años luego de la irradiación fueron 90 por ciento 100por ciento y 100 por ciento para pacientes tratados con radioterapia adyuvante, y 45 por ciento, 97 por ciento y 95 por ciento para los pacientes tratados con radioterapia de rescate, respectivamente. En estos últimos, cuando no se empleó hormonoterapia asociada, la comprobación de descenso del nivel de antígeno prot tico específico (PSA) a los 50 Gy orienta hacia un mejor control bioquímico. Las complicaciones tardías urinarias fueron m s frecuentes que cuando se emplea solamente la radioterapia como tratamiento radical de inicio.

Cáncer localizado de próstata: experiencia de diez años con radioterapia conformal tridimensional / Localized prostate cancer: ten year-experience of tridimensional conformal radiotherapy

Se analizaron 560 pacientes consecutivos con cáncer localizado de próstata tratados con radioterapia conformal tridimensional entre 1993 y 2001. La sobrevida global actuarial a los 9 años fue de 71 por ciento, y la sobrevida causa específica de 88 por ciento. La mortalidad cruda por cáncer de próstata fue de 4,8 por ciento mientras que la mortalidad por otras causas fue ded 8,3 por ciento. La sobrevida libre de recaída bioquímica en función del grgupo dee riesgo fue de 83 por ciento, 68 por ciento y 41 por ciento a los 9 años, respectivamente para los grupos de riesgo bajo, intermedio y alto en 504 pacientes (p<0,05). La dosis mayor o igual a 72 Gy mejora el control bioquímico a los 7 años en todos los grupos de riesgo aunque sólo es estadísticamente significativa en el grupo de riesgo alto (p<0,006). el modelo ded Cox reveló que solamente el grupo de riesgo, la dosis total como variable continua y el antígeno prostático específico inicial como variable categórica fueron significativos. Cuando el modelo de Cox fue aplicado a los 188 pacientes de reisgo alto, el uso de la hormonoterapia de inducción o concomitante, o ambas, y la edad, resultaron además significativos. La tasa actuarial de complicaciones severas a 10 años grados 3 y 4 (no hubo complicaciones grado 5) fue de 1,2 por ciento para las urinarias y de 1,4 por ciento para las digestivas. La radioterapia conformal tridimensional a altas dosis es un tratamiento efectivo y de baja morbilidad para el tratamiento del cáncer localizado de próstata.

Acute radiation reactions in oral and pharyngeal mucosa: tolerable levels in altered fractionation schedules.

PURPOSE: To investigate whether a predictive estimate can be obtained for a 'tolerance level' of acute oral and pharyngeal mucosal reactions in patients receiving head and neck radiotherapy, using an objective set of dose and time data. MATERIALS AND METHODS: Several dozen radiotherapy schedules for treating head and neck cancer have been reviewed, together with published estimates of whether they were tolerated or (in a number of schedules) not. Those closest to the borderline were given detailed analysis. Total doses and biologically effective doses (BED or ERD) were calculated for a range of starting times of cellular repopulation and rates of daily proliferation. Starting times of proliferation from 5 to 10 days and daily cellular doubling rates of 1-3 days were considered. The standard published form of BED with its linear overall time factor was used: BED=nd(1 + d/(alpha/beta) - Ln2(T - T(k))/alpha T(p) (see text for parameters). RESULTS: A clear progression from acceptable to intolerable mucosal reactions was found, which correlated with total biologically effective dose (BED in our published modeling), for all the head and neck cancer radiotherapy schedules available for study, when ranked into categories of 'intolerable' or 'tolerable'. A review of published mechanisms for mucosal reactions suggested that practical schedules used for treatment caused stimulated compensatory proliferation to start at about 7 days. The starting time of compensatory proliferation had little predictive value in our listing, so we chose the starting time of 7 days. Very short and very long daily doubling rates also had little reliability, so we suggest choosing a doubling time of 2.5 days as a datum. With these parameters a 'tolerance zone of uncertainty' could be identified which predicted acute-reaction acceptability or not of a schedule within a range of about 2-10 Gy in total BED. If concurrent chemoradiotherapy is used, our provisional suggestion is that this zone should be reduced by up to roughly 3-5 Gy10 in BED, with a request for further evidence. CONCLUSIONS: It is suggested that total BED should be used, as specified above. Parameters of alpha=0.35 Gy-(1), alpha/beta=10 Gy, Tk=7 days and Tp=2.5 days are suggested. The 'acute/ tolerance zone' then turns out to be 59-61 Gy10 for radiation-only treatments. Further information about the decrement caused by concurrent head-and-neck cancer chemoradiotherapy, possibly 3-5 Gy10, is required.

Treatment of breast abscesses with sonographically guided aspiration, irrigation, and instillation of antibiotics.

OBJECTIVE: We studied the feasibility of treating breast abscesses with sonographically guided aspiration, irrigation, and local instillation of antibiotics without placing indwelling catheters. MATERIALS AND METHODS: Seventy-three patients with breast abscesses were seen from 1995 to 2001. Aspiration and irrigation were performed under sonographic guidance. Repeated aspiration was performed when deemed necessary. One gram of cephradine was injected into 29 abscesses measuring more than 25 mm. RESULTS: Six patients refused further treatment after failure of the first aspiration and elected surgical drainage. Of the remaining 67 patients who completed treatment, 38 required one aspiration for cure, 18 required two aspirations, and eight required more than two aspirations. The treatment failed and surgical drainage was required in only three of the 67 patients completing treatment. CONCLUSION: Ninety-six percent of patients completing treatment were cured with this procedure. Local instillation of antibiotics is probably beneficial.

Revisiting the mammographic follow-up of BI-RADS category 3 lesions.

OBJECTIVE: Using data collected for one series during 1987-1989 and data collected for another series during 1996, we sought to compare the frequency of and positive predictive value for carcinoma of the breast in nonpalpable, probably benign lesions that had been detected on and followed up with mammography. MATERIALS AND METHODS: During 1996, mammography was performed in 18,435 women of whom 544 (3.0%) had lesions assigned to Breast Imaging Reporting and Data System (BI-RADS) category 3 for nonpalpable, probably benign lesions. The lesions in the women were assessed as BI-RADS category 3 after the patients had undergone a diagnostic study that included additional imaging, sonography, and a focused physical examination. Patients with BI-RADS category 3 lesions were recommended for mammographic surveillance. A minimum of 2 years of follow-up data was available for 511 patients, our study population. We compared the findings for our study population with those of the previous study. RESULTS: Ninety-seven percent of the follow-up mammograms showed stability or regression of the BI-RADS category 3 lesions. Fourteen patients (3%) had nonpalpable interval progression revealed on mammography and underwent biopsy. The breast cancer detection rate in category 3 lesions among the study population was 0.4% (2/511), which was 14% of the patients who had undergone biopsies because of interval progression of the lesions. The pathologic stage of the cancers in these two patients was T1b N0. CONCLUSION: Compared with the findings from the 1987-1989 study, the frequency of BI-RADS category 3 lesions has remained stable; patient compliance for follow-up has increased; and the positive predictive value of category 3 lesions for cancer has decreased from 1.7% to 0.4% (p = 0.04).

Cesium-137 needle brachytherapy boosts after external beam irradiation for locally advanced carcinoma of the tongue and floor of the mouth.

PURPOSE: A retrospective study was undertaken to compare local tumor control and complications of external beam radiation therapy with and without interstitial 137Cs needle brachytherapy boost doses. METHODS AND MATERIALS: Two hundred one consecutive patients with locally advanced (T3-T4) cancer of the tongue and floor of the mouth treated with definitive radiotherapy by external beam irradiation with (n = 78) or without (n = 123) low-dose-rate interstitial brachytherapy from 1974 to 1999 were analyzed retrospectively. External beam irradiation was administered with conventional fractionation in 105 patients and administered with accelerated hyperfractionation in 96 patients. RESULTS: The 8-year actuarial local control rates showed a trend toward improved results in the combined-treatment group as a whole and also when it was stratified into patients with base of tongue sites and those with oral tongue and floor of mouth sites. Cox regression analysis for local control showed that the only significant variable was overall treatment time. The use of brachytherapy boost doses was not a significant variable. The 8-year actuarial probability of Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Grades 3-5 late effects was 25% and 35% for patients with and without brachytherapy, respectively (p = not significant), although the crude incidence of mandibular radiation osteonecrosis was 10% and 1.6%, respectively (p =0.001). CONCLUSIONS: This study showed a trend toward improved local control rates for brachytherapy after external beam radiotherapy. The incidence of mandibular osteonecrosis was increased.