Sandra Jorcano

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

Abstract Background. Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. Material and methods. From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48–82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. Results. After a median follow-up of 31 months (range, 9–89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15–0.93). Conclusion. Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

Hypofractionated boost to the dominant tumor region with intensity modulated stereotactic radiotherapy for prostate cancer: a sequential dose escalation pilot study.

PURPOSE To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate. METHODS AND MATERIALS After conventional fractionated external radiotherapy to 64 to 64.4 Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60 cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7 Gy, respectively (normalized total dose in 2 Gy/fraction [NTD(2 Gy)] < 100 Gy, low-dose group), whereas 29 patients received two fractions of 8 Gy each (NTD(2 Gy) > 100 Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system. RESULTS Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of >or=Grade 2 late urinary and late low gastrointestinal (GI) toxicity-free survival were 82.2% +/- 7.4% and 72.2% +/- 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease-free survival (b-DFS) and disease-specific survival were 98% +/- 1.9% and 100%, respectively. CONCLUSION Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

Toxicity of combined treatment of adjuvant irradiation and interferon α2b in high-risk melanoma patients

Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) &agr;2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFN&agr;2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFN&agr;2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFN&agr;2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.

Twice-Weekly Hypofractionated Intensity-Modulated Radiotherapy for Localized Prostate Cancer With Low-Risk Nodal Involvement: Toxicity and Outcome From a Dose Escalation Pilot Study

PURPOSE To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk ≤20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). RESULTS All patients completed the treatment without interruptions. No patient presented with Grade ≥3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2% ± 2.9% and 96.1% ± 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% ± 5.9%, 76.4% ± 8.8%, and 77.5% ± 8.9% for low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

Dose-adapted salvage radiotherapy after radical prostatectomy based on an erMRI target definition model: Toxicity analysis

Abstract Background. To assess treatment tolerance by patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an multiparametric endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). Material and methods. A total of 171 prostate cancer patients recurring after RP undergoing erMRI before SRT were analyzed. A median dose of 64 Gy was delivered to the prostatic bed (PB) with, in addition, a boost of 10 Gy to the suspected relapse as visualized on erMRI in 131 patients (76.6%). Genitourinary (GU) and gastrointestinal (GI) toxicities were scored using the RTOG scale. Results. Grade ≥ 3 GU and GI acute toxicity were observed in three and zero patients, respectively. The four-year grade ≥ 2 and ≥ 3 late GU and GI toxicity-free survival rates (109 patients with at least two years of follow-up) were 83.9 ± 4.7% and 87.1 ± 4.2%, and 92.1 ± 3.6% and 97.5 ± 1.7%, respectively. Boost (p = 0.048) and grade ≥ 2 acute GU toxicity (p = 0.008) were independently correlated with grade ≥ 2 late GU toxicity on multivariate analysis. Conclusions. A dose-adapted, erMRI-based SRT approach treating the PB with a boost to the suspected local recurrence may potentially improve the therapeutic ratio by selecting patients that are most likely expected to benefit from SRT doses above 70 Gy as well as by reducing the size of the highest-dose target volume. Further prospective trials are needed to investigate the use of erMRI in SRT as well as the role of dose-adapted protocols and the best fractionation schedule.

Hypofractionated Extracranial Stereotactic Radiotherapy Boost For Gynecologic Tumors: A Promising Alternative To High-Dose Rate Brachytherapy

The purpose of this study is to report toxicity and outcome results in patients with gynaecological tumours treated with a final boost using extra-cranial stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9) cancer were treated according to this protocol: 45–50.4 Gy external radiotherapy (RT) to the pelvic ± para-aortic regions followed by a final SRT boost of 2 × 7 Gy to the vaginal vault (4–7 day interval between fractions). Median age was 62 years (37–74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n = 7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria. No severe (>grade-3) acute urinary or low-gastrointestinal (GI) toxicity was observed during treatment and up to 3 months after treatment completion. Moderate (grade ≤ 3) acute urinary or low-GI toxicity was observed in 23% and 35% of patients, respectively. After a median follow-up of 47 months (4–77, range), late urinary, low-GI, and sexual ≥grade-2 (worst score) has been reported in 4%, 12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free and overall survival rates were 96% and 95%, respectively. Preliminary results on feasibility, tolerance, and outcome with SRT are encouraging and may be considered a sound alternative to HDR-BT for gynecologic tumors.

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility, Tolerance and Outcome

AIMS To evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique. MATERIALS AND METHODS Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system. RESULTS All patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049). CONCLUSIONS The use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

IntroductionWhole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy.Materials and methodWe have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy.ResultsPrognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses.ConclusionsThe results suggest that MST was not significantly affected by the total dose/fractionation schedule.

Temozolomide as prophylaxis for melanoma brain metastases.

Departments of Radiation Oncology, Medical Oncology, Dermatology, Hospital Clinic, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain and Department of Dermatology, Hospital Arnau de Vilanova, Universitat de Lleida, Lieida, Spain. Correspondence to Susana Puig, Department of Dermatology, Hospital Clinic, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. Tel: + 34 93 2275438; fax: + 34 93 2275438; e-mail: spuig@clinic.ub.es

Long-term Results of a Comparative PET/CT and PET/MRI Study of 11 C-Acetate and 18 F-Fluorocholine for Restaging of Early Recurrent Prostate Cancer

Purpose The aims of this study were to assess the intraindividual performance of 18F-fluorocholine (FCH) and 11C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management. Methods Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA] ⩽3 ng/mL), primary radiotherapy (n = 8, prostate-specific antigen ⩽5 ng/mL), or radical prostatectomy + salvage radiotherapy (n = 15) underwent ACE and FCH PET-CT (n = 29) or PET-MRI (n = 4) studies in a randomized sequence 0 to 21 days apart. Results The detection rate for ACE was 66% and for FCH was 60%. Results were concordant in 79% of the cases (26/33) and discordant in 21% (retroperitoneal, n = 5; pararectal, n = 1; and external iliac nodes, n = 1). After a median FU of 41 months (n = 32, 1 patient lost to FU), the site of relapse was correctly identified by ACE and FCH in 53% (17/32) and 47% (15/32) of the patients, respectively (2 M1a patients ACE+/FCH−), whereas in 6 of 32 patients the relapse was not localized. Treatment approach was changed in 11 (34.4%) of 32 patients and 9 (28%) of 32 patients restaged with ACE and FCH PET, respectively. Conclusions In early recurrent PCa, ACE and FCH showed minor discrepancies, limited to nodal staging and mainly in the retroperitoneal area, with true positivity of PET findings confirmed in half of the cases during FU. Treatment approach turned out to be influenced by ACE or FCH PET studies in one third of the patients.