Morbidity dynamics in proton–photon or photon radiation therapy for locally advanced prostate cancer

Aim

This study evaluated the frequency and long-term dynamics of early and late post irradiation damage after proton–photon or photon therapy for locally advanced prostate cancer.

Prostate embryonal rhabdomyosarcoma in adults: Case report and review of literature

Introduction

Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, with a median occurrence age of 5 years, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethral obstruction, and systemic spread, commonly to the lungs, liver and bone. Several therapeutic approaches have been employed in the effort to treat prostate ERMS, but all of them have failed to gain a significant survival benefit in adult patients.

Case report

We report on a case of a stage IV prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), and, subsequent radiotherapy to the prostatic bed (60 Gy/30 fxs). The patient remained free of progression of disease for about 1 year to finally experience a systemic relapse with multiple lung metastases and pleural effusion. The patient died for metastatic disease 27 months following the initial diagnosis.

Conclusion

While it remains questionable which therapeutic approach for prostate ERMS in adults is the most appropriate, our report demonstrates that a chemo-radiation combined treatment can control the prostate disease, reducing the symptoms and improving the quality of life of these patients, for the most part destined to die for systemic progression of disease.     

Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy

ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4B^C74Ain vitro and in vivo, we show that the effects of ATG4B^C74A are cell type, treatment, and context-dependent. ATG4B^C74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response.     

Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy

AimThe purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients.BackgroundPrevious hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT.Materials and methodsWe evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04 Gy at 2.52 Gy/fraction (N = 25; 66%), 70 Gy at 2.5 Gy/fraction (N = 4; 11%) and 70.2 Gy at 2.6 Gy/fraction (N = 9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.ResultsMedian age at diagnosis was 70 years (range 49–80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P = 0.025). Patients with PSA ≤8 (P = 0.048) or comorbidities (P = 0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P = 0.028).ConclusionsHypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.     

Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in a series of 282 patients

Aim

To assess the outcomes of patients treated with postoperative RT in relation to the possible prognostic factors.

Background

Postoperative radiotherapy (RT) has been proved to reduce the risk of biochemical recurrence in high-risk prostate cancer patients. Baseline prostate specific antigen (PSA), pathological Gleason score (GS), positive surgical margins, nodal status and seminal vesicle invasion are independent predictors of biochemical relapse.

Materials and methods

The clinical records of 282 patients who underwent postoperative RT were retrospectively reviewed. The prognostic value of postoperative PSA, preoperative risk class, nodal status, pathological GS, margins status, and administration of hormonal therapy (HT) was analyzed.

Results

Postoperative RT was delivered with a median dose to the prostatic fossa of 66 Gy (range 50–72) in 1.8–2 Gy/fraction. Median follow-up was 23.1 months (range 6–119). Five-year actuarial biochemical disease-free survival (bDFS) and overall survival rates were 76% and 95%, respectively. Higher bDFS was found for patients with postoperative PSA <0.02 ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4–6 (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of surgical margin status (p = 0.10). Multivariate analysis showed that postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039 and p = 0.05, respectively).

Conclusions

Postoperative RT with a dose of 66 Gy offers an acceptable toxicity and an optimal disease control after radical prostatectomy in patients with different risk features. A postoperative PSA >0.02 ng/ml could be considered as a prognostic factor and a tool to select patients at risk for progression.     

Lower urinary tract infections from external beam radiation therapy in prostate cancer: A single institution experience

External beam radiation therapy (EMRT) is effective for the treatment of localized prostate cancer. Lower urinary tract infections (LUTIs) are considered one of the main possible adverse events related to External beam radiation therapy. Here we analyzed the incidence of LUTI during EMRT. Urinary tract infection was assumed when the findings of bacteriuria exceeded 100,000 units/mL, accompanied by specific cystitis symptoms. Among the total 540 analyzed patient, 208 (38.5%) developed a LUTI. E. coli was the main microorganism involved in LUTIs (102, 49.04%) with 8 cases of a combination between E. coli and another germ. In conclusion, a risk of urinary infections in cancer patients treated with pelvic radiotherapy was observed, in order to reduce the use of antibiotic resistance, preventive treatment with non-antibiotic agents 5 are warranted.     

Prostate cancer radiation therapy: A physician’s perspective

Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician’s perspective.     

Empirical estimation of beam-on time for prostate cancer patients treated on Tomotherapy

Background and aim

This study proposed a method to estimate the beam-on time for prostate cancer patients treated on Tomotherapy when FW (field width), PF (pitch factor), modulation factor (MF) and treatment length (TL) were given.

Material and methods

The study was divided into two parts: building and verifying the model. To build a model, 160 treatment plans were created for 10 patients. The plans differed in combination of FW, PF and MF. For all plans a graph of beam-on time as a function of TL was created and a linear trend function was fitted. Equation for each trend line was determined and used in a correlation model. Finally, 62 plans verified the treatment time computation model – the real execution time was compared with our estimation and irradiation time calculated based on the equation provided by the manufacturer.

Results

A linear trend function was drawn and the coefficient of determination R² and the Pearson correlation coefficient r were calculated for each of the 8 trend lines corresponding to the adequate treatment plan. An equation to correct the model was determined to estimate more accurately the beam-on time for different MFs. From 62 verification treatment plans, only 5 disagreed by more than 60 s with the real time from the HT software. Whereas, for the equation provided by the manufacturer the discrepancy was observed in 16 cases.

Conclusions

Our study showed that the model can well predict the treatment time for a given TL, MF, FW and it can be used in clinical practice.     

Potential interest of developing an integrated boost dose escalation for stereotactic irradiation of primary prostate cancer

IntroductionThe stereotactic irradiation is a new approach for low-risk prostate cancer. The aim of the present study was to evaluate a schema of stereotactic irradiation of the prostate with an integrated-boost into the tumor.Material and methodsThe prostate and the tumor were delineated by a radiologist on CT/MRI fusion. A 9-coplanar fields IMRT plan was optimized with three different dose levels: 1) 5 × 6.5 Gy to the PTV1 (plan 1), 2) 5 × 8 Gy to the PTV1 (plan 2) and 3) 5 × 6.5 Gy on the PTV1 with 5 × 8 Gy on the PTV2 (plan 3). The maximum dose (MaxD), mean dose (MD) and doses received by 2% (D2), 5% (D5), 10% (D10) and 25% (D25) of the rectum and bladder walls were used to compare the 3 IMRT plans.ResultsA dose escalation to entire prostate from 6.5 Gy to 8 Gy increased the rectum MD, MaxD, D2, D5, D10 and D25 by 3.75 Gy, 8.42 Gy, 7.88 Gy, 7.36 Gy, 6.67 Gy and 5.54 Gy. Similar results were observed for the bladder with 1.72 Gy, 8.28 Gy, 7.01 Gy, 5.69 Gy, 4.36 Gy and 2.42 Gy for the same dosimetric parameters. An integrated SBRT boost only to PTV2 reduced by about 50% the dose difference for rectum and bladder compared to a homogenous prostate dose escalation. Thereby, the MD, D2, D5, D10 and D25 for rectum were increased by 1.51 Gy, 4.24 Gy, 3.08 Gy, 2.84 Gy and 2.37 Gy in plan 3 compared to plan 1.ConclusionsThe present planning study of an integrated SBRT boost limits the doses received by the rectum and bladder if compared to a whole prostate dose escalation for SBRT approach.