Federica Gherardi

Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

PURPOSE To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. METHODS AND MATERIALS Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [(11)C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). RESULTS The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. CONCLUSIONS CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.

CORRELATION BETWEEN ACUTE AND LATE TOXICITY IN 973 PROSTATE CANCER PATIENTS TREATED WITH THREE-DIMENSIONAL CONFORMAL EXTERNAL BEAM RADIOTHERAPY

PURPOSE To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. METHODS AND MATERIALS Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. RESULTS Multivariate analysis showed that age </=65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). CONCLUSION The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

Linac-based stereotactic body radiotherapy for oligometastatic patients with single abdominal lymph node recurrent cancer

Objectives:To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. Methods:Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. Results:Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. Conclusions:SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation

OBJECTIVES To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. MATERIALS AND METHODS One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. RESULTS All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT (P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT (P = 0.001) and higher PSA (P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. CONCLUSIONS The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.

Image Guided Hypofractionated Radiotherapy and Quality of Life for Localized Prostate Cancer: Prospective Longitudinal Study in 337 Patients

PURPOSE We prospectively analyzed quality of life in a cohort of patients with prostate cancer undergoing a course of hypofractionated image guided radiotherapy. MATERIALS AND METHODS Between August 2006 and January 2011, 337 patients with a median age of 73 years who had cT1-T2N0M0 prostate cancer were eligible for this prospective, longitudinal study of hypofractionated image guided radiotherapy (70.2 Gy/26 fractions) using 1 of 3 image guided radiotherapy modalities (transabdominal ultrasound, x-ray or cone beam computerized tomography) available in our radiation oncology department. Patients completed 4 questionnaires before treatment, and 6, 12 and 24 months later, including the International Index of Erectile Function-5, International Prostate Symptom Score, and EORTC (European Organization for Research and Treatment of Cancer) prostate cancer specific QLQ-PR25 and QLQ-C30. RESULTS Patient followup was updated to at least the last questionnaire time point. Median followup was 19 months. Significant deterioration in erectile function on the International Index of Erectile Function-5 was documented with time only in patients without androgen deprivation (p = 0.0002). No change with time was observed in urinary symptom related quality of life on the QLQ-PR25 or International Prostate Symptom Score. Slight deterioration in QLQ-PR25 bowel symptom related quality of life was observed (p = 0.02). Overall QLQ-C30 Global Health Status improved with time (p = 0.03). On univariate analysis it significantly correlated with the maximum RTOG (Radiation Therapy Oncology Group)/EORTC urinary and bowel late toxicity scores after radiotherapy. CONCLUSIONS The regimen of hypofractionated image guided radiotherapy with multiple imaging modalities adopted in our radiation oncology department for localized prostate cancer might be a successful strategy for dose escalation with a limited impact on different aspects of quality of life with time.

Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer

OBJECTIVE To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). METHODS 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)). RESULTS Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. CONCLUSION re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. ADVANCES IN KNOWLEDGE Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

High-dose-rate interstitial brachytherapy in early stage buccal mucosa and lip cancer: report on the consecutive 12 patients and review of the literature

AIMS AND BACKGROUND To evaluate clinical outcome and toxicity using high-dose-rate brachytherapy as monotherapy in head and neck carcinomas. METHODS Between September 2004 and April 2010, a series of 12 patients with lip (7 patients) or buccal mucosa (5 patients) cancers were treated by exclusive interstitial high-dose-rate brachytherapy. The median age of the patients was 71.5 years (range, 47-87). Stages were T1N0M0 and T2N0M0 in 6 and 6 patients, respectively. A dose of 27 to 54 Gy in 9 to 16 fractions, 3 to 4.5 Gy per fraction, 2 fractions per day with a minimal gap of 6 h in between was delivered. RESULTS After a median follow-up of 46 months (range, 10-85), the disease-free and overall survival was 83% (10 of 12 patients) and 50% (6 of 12 patients), respectively. The crude local control in the lip cancer patients was 100% and in the buccal mucosa cancer patients was 60%. No severe toxicity was registered. CONCLUSIONS High-dose-rate brachytherapy is feasible and safe and offers the possibility to treat patients in an outpatient regimen.

Can the Day 0 CT-scan predict the post-implant scanning? Results from 136 prostate cancer patients

PURPOSE Post-implant CT-scanning is an essential part of permanent prostate brachytherapy. However, the evaluation of post-implant CT dosimetry is not straightforward due to the edema that can modify the dose to the prostate and to the organs at risk. The aim of this study is to evaluate the impact of the timing of the post-implant CT-scan on the dosimetric results and to verify if the Day 0 scan findings can predict Day 50 scanning. METHODS 136 consecutive patients who received monotherapy with I-125 implants were selected for this study. Two sets of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0 and Day 50) were calculated and compared. The dosimetric parameters included are the percentage volume of the post-implant prostate receiving 80%, 100% and 150% of the prescribed dose, the doses covering 80% and 90% of the prostate volume and the Dose Homogeneity Index. The values of the dose covering 1cm3 of the rectum and urethra were assessed. RESULTS All the dosimetric parameters of the Day 50 were higher than those of the Day 0 scan. Linear functions were obtained that calculate D90 and V100 values at Day 50 based on the Day 0 findings. Rectal and urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day 50 based dosimetry. CONCLUSIONS Predicting the Day 50 dosimetry from the Day 0 scan could be a possible alternative to a Day 50 scan only in specific situations, but with a degree of uncertainty in the predicted values.