Neighborhood Deprivation and Rurality Associated With Patient-Reported Outcomes and Survival in Men With Prostate Cancer in NRG Oncology RTOG 0415.

PURPOSE: Rurality and neighborhood deprivation can contribute to poor patient-reported outcomes, which have not been systematically evaluated in patients with specific cancers in national trials. Our objective was to examine the effect of rurality and neighborhood socioeconomic and environmental deprivation on patient-reported outcomes and survival in men with prostate cancer in NRG Oncology RTOG 0415. METHODS AND MATERIALS: Data from men with prostate cancer in trial NRG Oncology RTOG 0415 were analyzed; 1,092 men were randomized to receive conventional radiation therapy or hypofractionated radiation therapy. Rurality was categorized as urban or rural. Neighborhood deprivation was assessed using the area deprivation index and air pollution indicators (nitrogen dioxide and particulate matter with a diameter less than 2.5 micrometers) via patient ZIP codes. Expanded Prostate Cancer Index Composite measured cancer-specific quality of life. The Hopkins symptom checklist measured anxiety and depression. EuroQoL-5 Dimension assessed general health. RESULTS: We analyzed 751 patients in trial NRG Oncology RTOG 0415. At baseline, patients from the most deprived neighborhoods had worse bowel (P = .011), worse sexual (P = .042), and worse hormonal (P = .015) scores; patients from the most deprived areas had worse self-care (P = .04) and more pain (P = .047); and patients from rural areas had worse urinary (P = .03) and sexual (P = .003) scores versus patients from urban areas. Longitudinal analyses showed that the 25% most deprived areas (P = .004) and rural areas (P = .002) were associated with worse EuroQoL-5 Dimension visual analog scale score. Patients from urban areas (hazard ratio, 1.81; P = .033) and the 75% less-deprived neighborhoods (hazard ratio, 0.68; P = .053) showed relative decrease in risk of recurrence or death (disease-free survival). CONCLUSIONS: Patients with prostate cancer from the most deprived neighborhoods and rural areas had low quality of life at baseline, poor general health longitudinally, and worse disease-free survival. Interventions should screen populations from deprived neighborhoods and rural areas to improve patient access to supportive care services.

The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.

BACKGROUND: In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. METHODS: The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. FINDINGS: Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. INTERPRETATION: The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. FUNDING: National Cancer Institute.

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415.

PURPOSE/OBJECTIVE: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521). MATERIAL/METHODS: Treatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/ß = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUCvalidation) was within AUCtraining ±â€¯SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (pHL) > 0.05. RESULTS: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35 Gy, and acute GI toxicity (AUC = 0.59-0.63; p = 0.02-0.04). The two generalizable MVA models, i.e., D5%[Gy] with or without acute GI toxicity (AUCvalidation = 0.64, 0.65; p = 0.01, 0.03; pHL = 0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65 Gy to ≤62 Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUCtraining = 0.57; p = 0.07). CONCLUSION: Late GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.

Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy.

PURPOSE: This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss. METHODS AND MATERIALS: The study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT. RESULTS: For the purpose of this study, we considered an arbitrary 5 cm3 of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively. CONCLUSIONS: The anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

PURPOSE: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. PATIENTS AND METHODS: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). RESULTS: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. CONCLUSION: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.

Moderate hypofractionated external beam radiotherapy alone for intermediate risk prostate cancer: long term outcomes.

INTRODUCTION: To report long term toxicity and efficacy of patients with intermediate risk prostate cancer treated with moderate hypofractionated radiotherapy (HypoRT). MATERIALS AND METHODS: We studied the first consecutive 100 men with intermediate risk (stage T2b-T2c, or PSA = 10-20 ug/L, or Gleason score = 7) adenocarcinoma of the prostate treated between October 2002 and May 2010 in our institution with moderate HypoRT. Patients were treated using three-dimensional conformal HypoRT to a dose of 66 Gy in 22 daily fractions prescribed to the isocenter. Androgen suppression was not given to any patient. A uniform 7 mm margin was created around the prostate for the planning target volume. Daily ultrasound was used to guide the radiotherapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir PSA level plus 2 ng/m. RESULTS: After a median follow up time of 80 months (range: 7-152), the 8 year actuarial freedom from biochemical relapse survival rate was 90%. The 8 year cancer specific survival and overall survival rates were 96% and 84%, respectively. Only 2 patients died from prostate cancer. The worst grade ≥ 2 late genitourinary (GU) or gastrointestinal (GI) toxicities ever documented were 19% and 20%, respectively. At the last follow up the incidence of grade ≥ 2 late GI or GU toxicity was of only 2% and 3%, respectively. No grade 4 or 5 late toxicity was seen. CONCLUSION: Our long term experience with HypoRT delivering 66 Gy/22 fractions prescribed to the isocenter using three-dimensional conformal radiotherapy shows excellent tumor control with acceptable toxicity.

Role of radiotherapy in metastatic non-small cell lung cancer.

Radiotherapy has had important role in the palliation of NSCLC. Randomized trials tend to suggest that, in general, short regimens give similar palliation and toxicity compared to longer regimens. The benefit of combining chemotherapy to radiosensitize the palliative radiation treatment is an open question, but so far it has not been proved to be very useful in NSCLC. The addition of molecular targeted drugs to radiotherapy outside of approved regimens or clinical trials warrants careful consideration for every single case and probably should not be used as a routine management. Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) are modern techniques being used each time more frequently in the treatment of single or oligometastases. In general, they offer good tumor control with little toxicity (with a more expensive cost) compared to the traditionally fractionated radiotherapy regimens.

Hypofractionated intensity modulated radiation therapy in combined modality treatment for bladder preservation in elderly patients with invasive bladder cancer.

PURPOSE/OBJECTIVE(S): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. METHODS AND MATERIALS: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. RESULTS: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. CONCLUSIONS: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid cystectomy.

Reporting late rectal toxicity in prostate cancer patients treated with curative radiation treatment.

PURPOSE: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. METHODS AND MATERIALS: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. RESULTS: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. CONCLUSION: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients.

Impact of FDG-PET/CT on radiotherapy volume delineation in non-small-cell lung cancer and correlation of imaging stage with pathologic findings.

PURPOSE: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. METHODS AND MATERIALS: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. RESULTS: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. CONCLUSION: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible.

O uso de FDG-PET/TC scan no planejamento da radioterapia em câncer do pulmão não de pequenas células / Use of FDG-PET/CT scan in the planning of radiation therapy for non-small cell lung cancer

Radioterapia é uma importante alternativa de tratamento curativo em pacientes com câncer do pulmão não de pequenas células. Entretanto, pulmões são muito sensíveis à radiação e isto aumenta a importância em se delimitar o volume a ser irradiado com precisão. Ultimamente, a tomografia por emissão de pósitron (PET) e a tomografia computadorizada (TC) são feitas de forma combinada, e a literatura sugere que seu impacto no planejamento da radioterapia é significativo. Ao se utilizar exames de PET/TC no planejamento da radioterapia é importante reconhecer e adaptar-se às diferenças entre os equipamentos de diagnóstico e de tratamento. Este texto discute alguns dos problemas técnicos que devem ser resolvidos quando se incorpora PET no planejamento radioterápico.

Radiation therapy represents an important alternative for curative treatment of patients with nonsmall cell lung cancer. However, an accurate definition of the volume to be irradiated becomes even more important, considering that lungs are highly sensitive to radiation. Most recently, combined FDG-PET/CT scan has been utilized, and the literature reports its significant role in the planning of radiation therapy, since it seems to influence the target-volume delineation in cases of lung cancer. Differences between diagnostic and treatment equipments must be taken into consideration when FDG-PET/CT scan is utilized in the planning of radiation therapy. The present study discusses some of the many technical problems that must be solved when PET is incorporated into the planning of radiation therapy for non-small cell lung cancer.

Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer.

PURPOSE: Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation. MATERIALS AND METHODS: Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. RESULTS: Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade < or = 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. CONCLUSION: 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

Is there a detrimental effect of waiting for radiotherapy for patients with localized prostate cancer?

OBJECTIVE: To evaluate a possible deleterious effect of waiting time to radiotherapy on the biochemical relapse (BR) of patients with localized prostate cancer. PATIENTS AND METHODS: Patients included in this retrospective study had localized prostate adenocarcinoma treated with external-beam irradiation alone. Waiting time was defined as the interval between the first consultation and the first radiation treatment. BR was defined as 3 consecutive rises of prostatic specific antigen (PSA). Patients were split into 3 groups of waiting time: group A were treated within 40 days; group B waited 41 to 80 days; group C waited >80 days to receive radiotherapy. The effect of waiting on BR was estimated by the Kaplan-Meier method. Multivariate Cox proportional hazards modeling was adjusted for known prognostic factors. RESULTS: There were 289 patients who participated in the analysis. Median follow-up time was 6.1 year. Overall BR rate was 44% at 5 years. The median waiting time increased over the study period from 26 days in 1992 to 123 days in 2000. In adjusted multivariate analysis there was a nonsignificant higher risk of BR with waiting for 41 to 80 days (hazard ratio [HR] = 0.8; 95% confidence interval [CI] = 0.3-1.6) and for >80 days (HR = 0.6; 95% CI = 0.2-1.5) when compared with patients treated within 40 days after consultation. CONCLUSION: Delaying the start of radiotherapy showed little effect on the rate of BR in the group of 288 prostate cancer patients analyzed in this study.

Ultrasound-based image guided radiotherapy for prostate cancer: comparison of cross-modality and intramodality methods for daily localization during external beam radiotherapy.

PURPOSE: To compare two different ultrasound-based verification systems for prostate alignment during daily external beam radiation therapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: Prostate displacements were measured prospectively in 40 patients undergoing daily EBRT. Comparison was made between a system based on the cross-modality verification method (CMVM), which uses two different imaging modalities to assess organ motion, and a system based on the intramodality verification method (IMVM), which uses only one imaging modality for such assessment. A total of 217 CMVM and 217 IMVM displacements were collected within a minute of each other. In 10 patients, IMVM displacements were also compared with those measured by sequential CT scans. RESULTS: Analysis in the paired CMVM and IMVM displacements shows a significant mean difference of 0.9 +/- 3.3 mm in the lateral and 6.0 +/- 5.1 mm in the superoinferior directions (p < 0.0001), whereas no significant difference was detected in the anteroposterior direction between the two methods. Comparison of the computed tomography scan and IMVM measured displacements shows no significant difference between the two methods, with mean values of 0.2 +/- 1.7 mm in the lateral, -0.3 +/- 1.6 mm in the anteroposterior, and 0.1 +/- 1.4 mm in the superoinferior directions. CONCLUSIONS: A significant systematic difference exists between cross-modality and intramodality methods when assessing prostate alignment during daily EBRT. Because displacements assessed by IMVM are consistent with those assessed by computed tomography scan, a more accurate prostate alignment appears to be obtained when the IMVM method is used.

No immediate treatment after biochemical failure in patients with prostate cancer treated by external beam radiotherapy.

OBJECTIVES: The treatment of patients with asymptomatic prostate cancer with biochemical failure (BF) remains controversial. The early introduction of hormonal therapy causes important secondary effects and increases costs. Our general policy has been to follow-up patients with low prostate-specific antigen (PSA) levels and a long PSA doubling time without therapy. We report our experience using such an approach. METHODS: Between 1992 and 2000, 676 patients with localized prostate cancer were treated with radical radiotherapy, with or without adjuvant hormonal therapy at our institution. Asymptomatic patients with BF, no clinical evidence of metastatic disease, a low PSA level, and long PSA doubling time were considered for follow-up without immediate hormonal therapy. The prognostic factors such as stage and Gleason score were not considered when electing follow-up without additional therapy. The follow-up included at least two annual visits with physical examination and PSA determination. RESULTS: With a median follow-up of 85 months, 285 patients (42%) had BF. In 178 of these men, the rising PSA level was the only abnormality. Of these, 113 were followed up without additional therapy and 65 received hormonal therapy. Of the 113 patients in the untreated group, 101 (89%) were alive and asymptomatic at the last follow-up visit and 12 (11%) had died of causes other than prostate cancer. The long-term outcomes were similar in both groups. CONCLUSIONS: Expectant management, without initial hormonal therapy, may be a reasonable option for selected patients with prostate cancer who present with BF without metastatic disease after radical external beam radiotherapy. This decision is important because the early introduction of hormonal therapy is associated with side effects and is expensive.

Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer.

PURPOSE: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. METHODS AND MATERIALS: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached > or = 10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. RESULTS: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. CONCLUSIONS: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.

Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment

INTRODUCTION: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience. MATERIALS AND METHODS: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39 percent) cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA. RESULTS: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL) and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months). CONCLUSION: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are asymptomatic after radical external radiotherapy. This decision is important, since early introduction of hormones brings late effects and is expensive. Prospective and randomized studies are required to define this issue.

Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment.

INTRODUCTION: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience. MATERIALS AND METHODS: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39%) cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA. RESULTS: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL) and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months). CONCLUSION: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are asymptomatic after radical external radiotherapy. This decision is important, since early introduction of hormones brings late effects and is expensive. Prospective and randomized studies are required to define this issue.

Quimioterapia concomitante à radioterapia no tratamento adjuvante do câncer da mama localizado / Concomitant chemotherapy and radiotherapy in the adjuvant treatment of breast cancer

Introdução: o tratamento adjuvante do câncer da mama com freqüência envolve o uso de radio (RT) e quimioterapia (QT). A seqüência ideal desta combinação ainda não foi estabelecida. O atraso da RT pode permitir falha local; o atraso da QT pode permitir falha sistêmica. Um tratamento não deve prejudicar o outro. Este artigo relata nossa experiência com RT mais QT concomitantes. Material e Métodos: foi feita análise retrospectiva de pacientes com câncer da mama que receberam RT mais QT ao mesmo tempo, após a cirurgia (conservadora ou radical), tratadas entre jan/89 e jan/99. A RT não incluiu mamária interna e axila, e teve dose total de 50Gy. Durante a RT pacientes receberam 1 ou 2 ciclos de ciclofosfamida, methotrexate e 5 fluouracil (CMF). Foram avaliadas mudanças de dose, toxicidade, tolerância. Resultados: idade média de 44 anos; seguimento mediano de 33 meses. Cirurgia conservadora: 62 pts; mastectomia: 41 pts. Todas receberam o tratamento sem mudança de dose ou interrupção da RT. Quanto à QT, 10/103 pts receberam 10 por cento-20 por cento menos dose de QT. Não houve evidência de mudança em resultados cosméticos. Conclusão: resultados sobre demora no início de RT ou QT vêm de estudos retrospectivos e são conflitantes. Enquanto a seqüência ideal do uso de RT e QT está para ser definida, temos feito ambos os tratamentos ao mesmo tempo, com uso de CMF como esquema de QT, sem maiores mudanças de dose ou toxicidade de nenhum dos tratamentos. A idéia é não atrasar nenhum dos dois tratamentos, mas está para ser provado se esta alternativa traz benefícios significativos.

Metástase cerebral: tratamento paliativo com radiocirurgia / Brain metastasis: palliative treatment with radiosurgery

O artigo faz avaliaçäo de 52 pacientes com metástase cerebral tratados com radiocirurgia estereotática na Universidade McGill, em Montreal. A radiocirurgia foi realizada com a técnica dinâmica em que, ao mesmo tempo, giram a mesa e a cabeça do acelerador linear de 10 MV. Todos os pacientes (56 tratamentos ao todo) foram tratados com um único isocentro e uma dose única mediana de 1800cGy na periferia da metástase. Em 88 por cento dos casos a radiocirurgia foi usada após falha de tratamento radioterápico fracionado em todo cérebro. Todos os 52 casos tiveram avaliaçäo com CT pós radiocirurgia. O seguimento mediano foi de 6 meses (variou entre 1 e 37 meses e a taxa de resposta, parcial ou completa foi de 64 por cento. Apenas 4 pacientes (7 por cento) tiveram algum tipo de complicaçäo tardia relacionada ao tratamento. Estes achados väo de encontro com dados da literatura. A radiocirurgia é tratamento pouco agrassivo, bem tolerado e com alta taxa de resposta para lesöes locais e pode ser útil para pacientes selecionaods. O seu valor definitivo, como tratamento único ou combinado com radioterapia em todo cérebro, está sendo avaliado de forma prospectiva e randomizada