Predictive factors for response to salvage stereotactic body radiotherapy in oligorecurrent prostate cancer limited to lymph nodes: a single institution experience.

BACKGROUND: In patients presenting with limited nodal recurrence following radical prostatectomy (RP), stereotactic body radiotherapy (SBRT) results might improve with a better case selection. METHODS: Single-institution retrospective analysis of patients presenting with 1-3 lymph node (LN) recurrences (N1 or M1a) on 18F-Choline PET/CT. Prior therapy included radical prostatectomy (RP) ± salvage radiotherapy (RT), in absence of any systemic therapy. Outcome parameters were biochemical response (BR), time to biochemical recurrence (TBR) and time interval between SBRT and androgen deprivation therapy start (TADT). Time to event endpoints was analysed using Kaplan-Meier method. Potential prognostic factors were examined using univariate proportional hazards regression for TADT and logistic regression for BR. The optimal cut-off point for LN size was calculated using the Contal and O'Quigley method. RESULTS: 25 patients fulfilling study criteria were treated with SBRT from January 2010 to January 2015 and retrospectively analysed. Median follow up was 18 months and median LN diameter 10.5 mm. SBRT was delivered to a median dose of 36 Gy in three fractions (range: 30-45 Gy). BR was reached in 52% of cases. Median TBR was 11.9 months and significantly longer in patients with larger LN (Hazard ratio [HR] = 0.87, P = 0.03). Using 14 mm as cut off for LN, median TBR was 10.8 months for patients with small LN (18 patients), and 21.2 months for patients with large LN (6 patients) (P unadjusted = 0.009; P adjusted = 0.099). ADT was started in 32% of patients after a median follow-up of 18 months. CONCLUSIONS: For PCa patients with 1-3 LN recurrence after RP (± salvage RT), SBRT might result in a better biochemical control when delivered to larger sized (≥ 14 mm) LN metastases. This study is hypothesis generating and results should be tested in a larger prospective trial.

PET-CT guided SIB-IMRT combined with concurrent 5-FU/MMC for the treatment of anal cancer.

BACKGROUND: To evaluate local control (LC), survival and toxicity in anal cancer patients treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy at a single institution. MATERIAL AND METHODS: From August 2010 to May 2015, 26 patients were treated at our institution with IMRT and concurrent 5-fluorouracil/mitomycin-C (5-FU/MMC) for localized squamous cell carcinoma of the anal canal (SCCAC). Radiotherapy (RT) with 50.4-60 Gy was delivered with a sequential boost in 31%, and a simultaneous-integrated boost (SIB-IMRT) in 69% of cases. Initial staging was based on PET-CT and MRI. Clinical measures of interest were the influence of PET-CT on staging and treatment planning, LC, disease free survival (DFS), overall survival (OS), colostomy free survival (CFS) and toxicities. RESULTS: Median age was 61 years, 22 patients (85%) were female, and no patient was HIV-positive. The proportion of patients with stage I, II, IIIA and IIIB disease was 15%, 35%, 23% and 27%, respectively. PET-CT modified the extent of nodal disease in 9/23 cases (39%) and lead to major changes in treatment planning in 4/23 patients (17%). MRI was more accurate at identifying T4 disease. RT was delivered at full dose in 26 patients (100%) and chemotherapy in 22/26 patients (85%). Two patients (7.7%) required RT breaks. Median follow-up was 35 months [IQR: 19-52]. The 2-year LC, DFS, OS and CFS were 100%, 100%, 100% and 92%. Acute grade ≥3 dermatitis and diarrhea occurred in 73% and 8% of cases, respectively. Grade 3-4 neutropenia was seen in 10/23 patients (43%). Four patients (15%) developed chronic grade 2 GI toxicity. CONCLUSIONS: PET-CT provided additional information leading to major changes in treatment planning for 17% of patients. Considering our excellent outcomes, routine use of PET-CT as standard staging modality and IMRT planning procedure appears justified for patients with SCCAC.

Correction to: ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial.

Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.

ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with localized prostate cancer. Promising results in terms of disease control and toxicity have been reported with 4 to 5 SBRT fractions. However, question of how far can the number of fractions with SBRT be reduced is a challenging research matter. As already explored by some authors in the context of brachytherapy, monotherapy appears to be feasible with an acceptable toxicity profile and a promising outcome. The aim of this multicenter phase I/II prospective trialis to demonstrate early evidence of safety and efficacy of a single-fraction SBRT approach for the treatment of localized disease. METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone will be treated with a single SBRT fraction of 19 Gy to the whole prostate gland with urethra-sparing (17 Gy). Intrafractional motion will be monitored with intraprostatic electromagnetic transponders. The primary endpoint of the phase I part of the study will be safety as assessed by CTCAE 4.03 grading scale, while biochemical relapse-free survival will be the endpoint for the phase II. The secondary endpoints include acute and late toxicity, quality of life, progression-free survival, and prostate-cancer specific survival. DISCUSSION: This is the first multicenter phase I/II trial assessing the efficacy and safety of a single-dose SBRT treatment for patients with localized prostate cancer. If positive, results of ONE SHOT may help to design subsequent phase III trials exploring the role of SBRT monotherapy in the exclusive radiotherapy treatment of localized disease. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03294889 ; Registered 27 September 2017.

Treatment of penile carcinoma: to cut or not to cut?

PURPOSE: The aim of this study was to assess the outcome in patients with penile cancer. METHODS AND MATERIALS: A total of 60 patients with penile carcinoma were included. Of the patients, 45 (n = 27) underwent surgery, and 51 underwent definitive (n = 29) or postoperative (n = 22) radiotherapy (RT). Median follow-up was 62 months. RESULTS: Median time to locoregional relapse was 14 months. Local failure was observed in 3 of 23 patients (13%) treated with surgery with or without postoperative RT vs. in 19 of 33 patients (56%) given organ-sparing treatment (p = 0.0008). Of 22 local failures, 16 (73%) were salvaged with surgery. Of the 33 patients treated with definitive RT (n = 29) and the 4 patients refusing RT after excisional biopsy, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 4 patients with local failure underwent salvage conservatively, resulting in an ultimate penis preservation rate of 17 of 33 (52%) patients treated with definitive RT. The 5-year and 10-year probability of surviving with an intact penis was 43% and 26%, respectively. There was no survival difference between the patients treated with definitive RT and primary surgery (56% vs. 53%; p = 0.16). In multivariate analysis, independent factors influencing survival were N-classification and pathologic grade. Surgery was the only independent predictor for better local control. CONCLUSION: Based on our study findings, in patients with penile cancer, local control is superior with surgery. However, there is no difference in survival between patients treated with surgery and those treated with definitive RT, with 52% organ preservation.

Impact of visceral fat volume and fat density on biochemical outcome after radical prostatectomy and postoperative radiotherapy.

BACKGROUND: To assess the predictive value of visceral adipose tissue (VAT) and adipose tissue density after both radical prostatectomy (RP) and adjuvant or salvage external beam radiotherapy (EBRT). MATERIALS AND METHODS: We randomly selected 201 patients treated with RP and EBRT between 2005 and 2015. Visceral adipose tissue and subcutaneous adipose tissue volumes were manually contoured and corresponding tissue densities in Hounsfield units (HU) calculated. Time to biochemical recurrence (BCR) was calculated using the Kaplan-Meier method and comparisons were made using the log-rank test. Cox regression analysis was done for multivariate analysis. RESULTS: Median time to BCR or last follow-up was 32 months. In univariate analysis for BCR, VAT volume and fat density were both associated with a better outcome (p=0.025 and p=0.024, respectively) as well as seminal vesicle involvement (p=0.024). Body mass index (BMI) was not predictive of BCR (p=0.32). In a multivariate model including seminal vesicle involvement, both a VAT volume above the median (HR2.5, 95%CI 1.1-5.7, p=0.03) and a VAT density (HR 2.4, 95%CI 1.1-5.1, p=0.028) above the median remained predictive for a better biochemical outcome. Adjusting for BMI did not significantly change the model. CONCLUSIONS: In both univariate and multivariate analysis, patients with both a larger VAT volume and density had a better biochemical outcome. The interaction between prostate cancer aggressiveness and visceral fat volume and density needs to be further evaluated to provide a better understanding of this disease.

Radiotherapy for Non-Hodgkin's lymphoma: still standard practice and not an outdated treatment option.

Two large, recently published observational studies demonstate a clear down-trend in the use of radiotherapy (RT) over the last 15 years, both in the setting of follicular and diffuse large B-cell lymphoma. This change of practice might have a negative impact on clinical outcome. Even within the context of modern systemic therapy, omission of RT translates not only into a shorter progression-free survival (PFS), but also into a worse overall survival (OS). RT should therefore remain standard practice.This short review is aiming to summarize current guidelines and the best evidence available in the management of non-Hodgkin's lymphoma. Potentially practice changing, ongoing trials will be highlighted.

CAPRA-S predicts outcome for adjuvant and salvage external beam radiotherapy after radical prostatectomy.

INTRODUCTION: We aimed to evaluate the predictive value of the Cancer of the Prostate Risk Assessment Postsurgical Score (CAPRA-S) for patients treated with radical prostatectomy followed by subsequent external beam radiotherapy (EBRT). METHODS: A total of 373 patients treated with EBRT between January 2000 and June 2015 were identified in the institutional database. Followup and complete CAPRA-S score were available for 334 (89.5%) patients. CAPRA-S scores were sorted into previously defined categories of low- (score 0-2), intermediate- (3-5), and high-risk (6-12). Time to biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) >0.20 ng/mL after EBRT. Survival analyses were performed using the Kaplan-Meier method and comparisons were made using the log-rank test. RESULTS: Overall median time from surgery to EBRT was 18 months (interquartile range [IQR] 8-36) and median followup since EBRT was 48 months (IQR 28-78). CAPRA-S predicted time to BCR (<0.001), time to palliative androgen-deprivation therapy (ADT) (p=0.017), and a trend for significantly predicting overall survival (OS, p=0.058). On multivariate analysis, the CAPRA-S was predictive of time to BCR only (low-risk vs. intermediate-risk; hazard ratio [HR] 0.14, 95% confidence interval [CI] 0.043-0.48, p=0.001). The last PSA measurement before EBRT as a continuous and grouped variable proved highly significant in predicting all outcomes tested, including OS (p≤0.002). CONCLUSIONS: CAPRA-S predicts time to BCR and freedom from palliative ADT, and is borderline significant for OS. Together with the PSA before EBRT, CAPRA-S is a useful, predictive tool. The main limitation of this study is its retrospective design.

[PET contribution in oncology]. / Apport du PET en oncologie.

Initial workup in oncology relies on histology and extensive staging of disease. Assessment of treatment response is also of paramount importance. Functional imaging with PET provides substantially more information than conventional radiology based on anatomic structures. PET applications in oncology are rapidly growing. We review herein the established and investigational indications for PET imaging, and also highlight some of its limitations.

Radiation therapy after radical prostatectomy: A single-centre radiation oncology experience in trends of referral and treatment practices.

INTRODUCTION: Our objective was to assess whether referral and treatment practices have changed since publication of the Southwest Oncology Group (SWOG) 8794 Trial in 2009, the first randomized study to demonstrate an overall survival advantage of adjuvant radiation therapy (RT) after radical prostatectomy (RP). METHODS: We retrospectively reviewed all medical charts of men who received RT at our institution between 2004 and 2014 following RP. All RT was conducted by a single radiation oncologist (DT). We divided the cohort into 2 groups according to first referral date before or after the SWOG 8794 trial publication (i.e., before 2010 and after 2010). RESULTS: Medical charts were available for 161/165 patients (97.6%). RP was performed at the same institution in 58% of cases. The median time between surgery and first referral for RT decreased significantly from 672 days (interquartile range [IQR] 295-1449) before 2010 to 300 days (IQR 225-1023) after 2010 (p = 0.04). This trend was associated with lower median prostate-specific antigen (PSA) at RT referral (0.26 µg/L [IQR 0.17-0.48] vs. 0.46 µg/L [IQR 0.25-0.90], respectively; p = 0.001). Androgen-deprivation therapy with RT nearly tripled over time from 13% before 2010 to 37% after 2010 (p = 0.003). Throughout the study period, the time interval between surgery and RT initiation was positively correlated with pT-stage (p = 0.001), Gleason score (p = 0.005) and PSA doubling time (p < 0.001). CONCLUSIONS: At our tertiary-referral academic institution, post-RP patients are notably referred earlier for RT and at lower PSA values compared to men treated prior to 2010. Further study is necessary to evaluate this impact on biochemical recurrence-free survival.

[Radio-chemotherapy in head and neck cancer (EGFR+)]. / Radiochimiothérapie dans les cancers ORL (EGFR+).

Squamous-cell carcinoma of the head and neck are neoplasic diseases for which locoregional control remains very important, given its particular pattern of failure. Treatment of early stage disease involves surgery or radiation therapy. Locally advanced disease is treated either with concurrent chemoradiotherapy or surgery followed by radio-chemotherapy, according to each center's expertise. Recent research has demonstrated that the overexpression of epidermal growth factor receptor (EGFR) is associated with tumor progression. Based on this research, a new type of anticancer therapy, so-called "targeted therapies" represent important additions to the current therapeutic arsenal in the management of head and neck cancers, based on results of a phase III trial combining radiotherapy and immunotherapy with cetuximab.

The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications.

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptors. Its stimulation by endogenous ligands, EGF or transforming growth factor-alpha (TGF-alpha) results in activation of intracellular tyrosine kinase, therefore, cell cycle progression. High levels of EGFR expression are correlated with poor prognosis and resistance to radiation therapy in a variety of cancers, mostly in squamous-cell carcinoma of the head and neck (SCCHN). Blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The EGFR is a prime target for new anticancer therapy in SCCHN, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies.