Andrei Fodor

Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

PURPOSEnTo present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer.nnnMETHODS AND MATERIALSnFive hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months.nnnRESULTSnAcute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed (p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity.nnnCONCLUSIONSnThree-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

PurposeTo test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM).Patients and MethodsA group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV).ResultsGood dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2–10 weeks. Median overall survival was 8 months (1.2–50.5 months) and 20 months (4.3–33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003).ConclusionsThe results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.ZusammenfassungZweckPrüfung der Machbarkeit von Salvage-Strahlentherapie mit der Hilfe PET-geführter helikaler Tomotherapie bei Patienten mit progredientem malignem Pleuramesotheliom (MPM).Patienten und MethodenDie erste Gruppe von 12 aufeinanderfolgenden MPM-Patienten wurde mit 56 Gy/25 Fraktionen im Planungszielvolumen behandelt. Eine FDG-PET/CT-Simulation wurde stets durchgeführt, um alle positiven Lymphknoten und MPM-Infiltrationen einzuschließen. Danach wurde eine zweite Gruppe von 12 aufeinanderfolgenden Patienten mit der gleichen Dosis auf der gesamten Pleura behandelt mit gleichzeitigem integriertem Boost von 62,5 Gy auf die FDG–PET/CT-positiven Bereiche (BTV).ErgebnisseGute dosimetrische Ergebnisse wurden in beiden Gruppen erzielt. In der ersten Gruppe wurde keine akute oder späte Grad-3-Toxizität (RTOG / EORTC) berichtet, während drei Fälle von später Grad-3-Pneumonitis in der zweiten Gruppe auftraten. Die Symptome hielten 2 bis 10 Wochen an. Das mediane Gesamtüberleben betrug 8 Monate (1,2–50,5 Monate) und 20 Monate (4,3–33,8 Monate) ab Therapiebeginn in Gruppe I und II (p = 0,19). Es wurde signifikanter Einfluss der Strahlentherapie auf Lokalrezidive beobachtet (mediane Zeit bis zum Lokalrezidiv: 8 vs 17 Monate; Rate 1-jähriger Lokalrezidivfreiheit: 16% vs 81%, p = 0,003).SchlussfolgerungenDie Ergebnisse dieser Pilotstudie sprechen für die Planung einer Phase-III-Studie der kombinierten sequentiellen Radiochemotherapie mit Dosiseskalation auf BTV bei inoperablen Patienten.

Salvage therapy of small volume prostate cancer nodal failures: A review of the literature

New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse (oligo-recurrent) potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.

Toxicity and efficacy of salvage carbon 11‐choline positron emission tomography/computed tomography‐guided radiation therapy in patients with lymph node recurrence of prostate cancer

To report the 3‐year toxicity and outcomes of carbon 11 (11C)‐choline‐positron emission tomography (PET)/computed tomography (CT)‐guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi‐Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer.

BENEFIT ON BIOCHEMICAL CONTROL OF ADJUVANT RADIATION THERAPY IN PATIENTS WITH PATHOLOGICALLY INVOLVED SEMINAL VESICLES AFTER RADICAL PROSTATECTOMY

Aims and Background To determine whether there is a benefit for biochemical control with adjuvant radiation therapy to the surgical bed following radical prostatectomy in patients with seminal vesicle invasion and pathologically negative pelvic lymph nodes (pT3b-pT4 pN0). Methods We retrospectively reviewed the clinical records of radical prostatectomy patients treated between 1995 and 2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of these patients received adjuvant radiation therapy and 21 were observed. Radiation therapy was initiated within 4 months of prostatectomy. Median dose was 66 Gy (range, 60–70 Gy). Median follow-up from the day of surgery was 40.6 months (mean, 41.5; range, 12–99). Biochemical recurrence was defined as the first value ≥0.2 ng/ml. Results At two years, the proportion of patients free from biochemical recurrence was 80% in patients who received adjuvant radiation therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no radiation therapy groups, respectively. On univariate Cox regression model, the hazard of biochemical failure was also associated with a detectable (≥0.2 ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason pattern and positive surgical margins were not significantly associated with biochemical recurrence. The hazard of biochemical failure was around 85% lower in the radiation therapy group than in the observation group (P = 0.002). Conclusions Data from the present series suggest that adjuvant radiation therapy for patients with seminal vesicle invasion and undetectable (≤0.2 ng/ml) postoperative prostate-specific antigen significantly reduces the likelihood of biochemical failure.

Megavoltage CT images of helical tomotherapy unit for radiation treatment simulation: impact on feasibility of treatment planning in a prostate cancer patient with bilateral femoral prostheses.

Metal prosthesis artefacts on CT images can be a significant problem in the definition of volumes of interest, dose calculation and patient setup in modern radiotherapy. We experienced considerable difficulties in defining the organs at risk and treatment volumes on kVCT images of standard CT simulation in a prostate cancer patient due to the presence of bilateral femoral prostheses causing artefacts. As shown in the current case, MVCT images of the patient in the treatment position obtained using a helical tomotherapy unit can provide sufficient morphological information to define the pelvic anatomic structures for radical prostate treatment planning. The patient completed the planned treatment and at 90 days after the end of treatment no severe side effects were recorded. Since there have been few reports on the use of MVCT images to overcome the problem of hip prosthesis artefacts, a brief literature review was also carried out.

Androgen ablation therapy does not increase the risk of late morbidity following 3D-conformal radiotherapy of organ-confined prostate cancer: The experience of the European Institute of Oncology

Aims and Background Androgen ablation therapy in conjunction with radiotherapy-neoadjuvant and adjuvant – has consistently been shown to be associated with improved biochemical and local control, whereas controversy still remains as regards its benefit in terms of overall survival. The objective of this study is to determine the impact of androgen ablation in combination to 3D-conformal radiotherapy on late treatment-related toxicity. Methods 236 patients were treated with 3D-conformal radiotherapy to a total dose ranging from 70 and 78.6 Gy. Fifty-six patients did not receive any form of androgen ablation whereas 176 were given at least 3 months of neoadjuvant androgen ablation. Of these, 64 stayed on androgen ablation for a median time of 6 months post-radiotherapy. Acute toxicity was evaluated weekly during the course of treatment. Late toxicity was assessed at 3-months intervals during the follow-up. Toxicity was scored according to the RTOG criteria. Results The median follow-up was 24.6 months (range, 12-62). The incidence of late genitourinary toxicity was: 3% G2, 3.5% G3, 0.5% G4. The incidence of late gastrointestinal toxicity was: 12% G2, 2% G3, 1% G4. No association was observed between the use of androgen ablation and late treatment-related toxicity. High-risk patients who continued on androgen ablation long-term were not found to have an increased risk of developing late toxicity with respect to those who never had any form of androgen ablation or those only treated neoadjuvantly. Conclusions In our experience, the use of androgen ablation does not impact on late toxicity following high dose 3D-conformal radiotherapy for prostate cancer.

The relationship between local recurrences and distant metastases in prostate cancer: can 11 C-choline PET/CT contribute to understand the link?

PurposePrevious studies in prostate cancer (PCa) patients tried to correlate the onset of local recurrence (LR) with the development of distant metastases and formulated, based on theoretical and experimental data, hypotheses linking the two events. We aimed to address this issue with 11C-choline positron emission tomography/computed tomography (PET/CT).MethodsThis retrospective study included 491 PCa patients previously treated with radical prostatectomy who had undergone 11C-choline PET/CT owing to biochemical failure. Further inclusion criteria were availability of clinical and pathological variables for survival analysis. Statistical significance was taken at Pu2009<u20090.05.ResultsSeventy-two patients (14.7%) had evidence of LR at 11C-choline PET/CT. The frequency of LR increased from 13.8% in the interval 0–4xa0years after prostatectomy, to 23.9% in the 12–16-year interval (Pu2009=u20090.080). On the contrary, the frequency of lymph node metastases (overall rate in the 0–16xa0years interval after prostatectomy: 26.3%) and of bone metastases (overall rate: 13.8%) decreased significantly over time. Kaplan-Meier curves showed no significant group difference in the rates of lymph node or bone metastases between patients with LR and patients without LR. LR significantly predicted PCa-specific survival at univariate analysis, but the statistical significance was lost at multivariate analysis.ConclusionWe found no differences in the rates of lymph node and bone metastases between patients with and without LR. An inverse time-dependent trend was observed in the frequency of LR on one side and of lymph node and bone metastases on the other side. These findings were discussed in relation to previous theories linking LR to distant metastases and our study design.

Oligorecurrent prostate cancer limited to lymph nodes: getting our ducks in a row

PurposeOligorecurrent prostate cancer with exclusive nodal involvement represents a common state of disease, amenable to local therapy. New radio-labeled tracers have enriched the possibility of cancer detection and treatment. In this review, we aim to illustrate the main nuclear medicine diagnostic options and the role of radiotherapy in this setting of patients.MethodsWe performed a PubMed search referring to the PRISMA guidelines to analyze the performance of PSMA- and choline-PET in detecting oligorecurrence limited to lymph nodes, and to review the main studies supporting either ablative stereotactic body radiotherapy or regional lymph node irradiation in this clinical setting.ResultsPSMA-PET has shown higher efficacy in the diagnosis of nodal lesions if compared with choline-PET. More specifically, for PSA ≤u20092xa0ng/ml, the median detection rate of choline-PET ranges from 19.5 to 44.5%, whereas PSMA ranges from 51.5 to 74%. SBRT achieves high local control rates positively affecting progression-free survival (PFS), with androgen deprivation therapy (ADT)-free survival ranging from 25 to 44xa0months and with low toxicity rates (0–15%). Prophylactic nodal irradiation shows 3-year PFS rates ranging from 62 to 75%, but with a potential higher risk of toxicity. However, the chosen treatment option needs to be tailored on the single patient.ConclusionsNewer PET/CT radio-labeled tracers have increased disease detection in oligorecurrent prostate cancer patients. Growing evidence of their impact on metastasis-directed therapy encourages the use of the most advanced radiotherapy techniques in the clinical management of such patients.

Moderately Hypofractionated Helical IMRT, FDG–PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

Introduction: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity‐modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose‐positron emission tomography (FDG‐PET) positive areas (gross tumor volume [GTV]‐PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. Methods and Materials: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6‐82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0‐18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG‐PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV‐PET was added in 38 patients. Results: The median survival from diagnosis was 25.8 months (range, 8.4‐99.0 months). One patient, treated with SIB, was alive at the October 2017 follow‐up. Two cases of grade 5 radiation pneumonitis were registered. A GTV‐PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV‐PET ≥ 473 cc was predictive of early death (P = .001). Conclusions: Moderately hypofractionated, FDG‐PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.