Dario Aiello

Hippocampal dose during Linac-based stereotactic radiotherapy for brain metastases: An observational study

INTRODUCTION Aim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM). MATERIALS & METHODS Patients with BM<5, size≤30mm, KPS≥80 and a life expectancy>3months, were considered for SRS/FSRT (total dose 15-30Gy, 1-5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed. RESULTS From April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C-H, the average Dmedian, Dmean and D0.1cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction. CONCLUSION During FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS.

Increased efficacy of stereotactic ablative radiation therapy after bevacizumab in lung oligometastases from colon cancer

Aim: Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods: The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months’ follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered. Results: A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001). Conclusions: In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.

Re: Giorgio Gandaglia, Alberto Briganti, Noel Clarke, et al. Adjuvant and Salvage Radiotherapy after Radical Prostatectomy in Prostate Cancer Patients. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2017.01.039

We read with interest the recent review by Gandaglia et al [1]. The authors affirm that immediate adjuvant radiation therapy (RT) following radical prostatectomy (RP) is associated with an increase in the incidence of shortand long-term side effects. To date, the issue of the role of adjuvant RT versus early salvage RT after RP in patients with adverse pathologic features has been widely debated [2]. Unfortunately, the literature lacks mature findings from well-designed randomized studies prospectively comparing adjuvant RT versus salvage RT after RP. In the era of personalized medicine, we believe that further trials are strongly warranted to identify ‘‘high-risk’’ prostate cancer (PC) patients who could really benefit from adjuvant RT [2]. In the near future, results from the ongoing RAVES phase 3 randomized controlled trial could help clinicians in decision-making after RP on the basis of a patient’s pathologic features. The RAVES trial is testing the hypothesis that observation with early salvage RT is not inferior to adjuvant RT with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins after RP. Thus, appropriate selection of PC patients for adjuvant versus early salvage RT remains an open issue. Another crucial question that remains unresolved is whether the toxicity related to adjuvant postoperative RT, as outlined by Gandaglia et al, is reliable in the modern era of intensity-modulated RT (IMRT) and image-guided RT (IGRT). First, the cited series do not give any information about the doses received by the bladder. As clearly stated in Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC), the risk of late severe bladder toxicity is related not only to the maximal dose (which should be <65 Gy) but also the dose to subvolumes of the bladder receiving a given dose level.

Re: Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, et al. Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage. Eur Urol 2017;71:37–43

We read with interest the article by Spratt and colleagues [1] recently published in European Urology. The authors analyzed patterns of abdominopelvic lymph node (LN) failure via radiographic LN mapping in a large series of prostate cancer (PC) patients treated with definitive doseescalated radiation therapy (RT) without pelvic LN RT. In their experience, radiographic failures were most frequently found above the L5/S1 landmark. Thus, for selected PC patients, the current pelvic LN RT recommendation could be revisited. The authors state that androgen deprivation therapy could prevent or minimize marginal and/or out-of-field recurrences. Moreover, Spratt et al [1] recommended revisiting of the current RT field recommendation for pelvic LNs (up to the superior border of the internal/external iliac vessels) because of inadequate RT coverage. Looking at their findings [1], a type of pelvic RT volume customization could be introduced in clinical practice. In fact, in the analysis by Spratt et al [1], PC patients with Gleason score 8 were at particular risk of dissemination to distant nodes. However, this PC category deserves accurate pre-RT staging to exclude distant dissemination [2]. Recent data support the value of molecular imaging in the therapeutic approach to high-risk PC. The reliability of new tracers (such as Cand F-choline and/or Galabeled prostate-specific membrane antigen [PSMA]) for PC has been investigated in several series [3]. While choline positron emission tomography (PET) is not indicated for routine local tumor staging, it seems to have better performance than conventional morphological imaging in LN staging and for all PC patients with suspected distant

Re: Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, et al. Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage. Eur Urol 2017;71:37–43: A Step Forward in the Era of Functional Imaging?

We read with interest the article by Spratt and colleagues [1] recently published in European Urology. The authors analyzed patterns of abdominopelvic lymph node (LN) failure via radiographic LN mapping in a large series of prostate cancer (PC) patients treated with definitive doseescalated radiation therapy (RT) without pelvic LN RT. In their experience, radiographic failures were most frequently found above the L5/S1 landmark. Thus, for selected PC patients, the current pelvic LN RT recommendation could be revisited. The authors state that androgen deprivation therapy could prevent or minimize marginal and/or out-of-field recurrences. Moreover, Spratt et al [1] recommended revisiting of the current RT field recommendation for pelvic LNs (up to the superior border of the internal/external iliac vessels) because of inadequate RT coverage. Looking at their findings [1], a type of pelvic RT volume customization could be introduced in clinical practice. In fact, in the analysis by Spratt et al [1], PC patients with Gleason score 8 were at particular risk of dissemination to distant nodes. However, this PC category deserves accurate pre-RT staging to exclude distant dissemination [2]. Recent data support the value of molecular imaging in the therapeutic approach to high-risk PC. The reliability of new tracers (such as Cand F-choline and/or Galabeled prostate-specific membrane antigen [PSMA]) for PC has been investigated in several series [3]. While choline positron emission tomography (PET) is not indicated for routine local tumor staging, it seems to have better performance than conventional morphological imaging in LN staging and for all PC patients with suspected distant

Induction chemotherapy for nasopharyngeal cancer: An eternally unfinished issue?

We read with interest the phase III randomised multicentric trial recently published by Su-Mei Cao et al. on European Journal of Cancer [1]. According to trial’s results [1], neoadjuvant chemotherapy (NACT) followedby concurrent chemoradiotherapy (CCRT) achieved higher 3-year disease-free survival than concurrent CCRT alone. However, no statistically significant differences in overall survival (OS) or loco-regional relapse-free survival were reported between the two arms. Paradoxically, Su-Mei Cao et al [1] concluded that the approach of ‘NACT followed by concurrent CCRT improved tumour control compared with CCRT alone in loco-regionally advanced nasopharyngeal cancer, particularly at distant sites’. From our point of view, the message by the Su-MeiCao et al [1] deserve tobemitigated. In fact, several points of the trial [1] need to be deeply criticised. First, in the study by Su-MeiCao et al. [1], 62.6% of the patients in theCCRTgroup comparedwith 51.3% in the investigational arm were submitted to 2D-irradiation. It is well recognised that intensity-modulated radiotherapy (IMRT) represents the standard of care in head and neck

Re: Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, et al. Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.07.043: A Step Forward in the Era of Functional Imaging?

We read with interest the article by Spratt and colleagues [1] recently published in European Urology. The authors analyzed patterns of abdominopelvic lymph node (LN) failure via radiographic LN mapping in a large series of prostate cancer (PC) patients treated with definitive doseescalated radiation therapy (RT) without pelvic LN RT. In their experience, radiographic failures were most frequently found above the L5/S1 landmark. Thus, for selected PC patients, the current pelvic LN RT recommendation could be revisited. The authors state that androgen deprivation therapy could prevent or minimize marginal and/or out-of-field recurrences. Moreover, Spratt et al [1] recommended revisiting of the current RT field recommendation for pelvic LNs (up to the superior border of the internal/external iliac vessels) because of inadequate RT coverage. Looking at their findings [1], a type of pelvic RT volume customization could be introduced in clinical practice. In fact, in the analysis by Spratt et al [1], PC patients with Gleason score 8 were at particular risk of dissemination to distant nodes. However, this PC category deserves accurate pre-RT staging to exclude distant dissemination [2]. Recent data support the value of molecular imaging in the therapeutic approach to high-risk PC. The reliability of new tracers (such as Cand F-choline and/or Galabeled prostate-specific membrane antigen [PSMA]) for PC has been investigated in several series [3]. While choline positron emission tomography (PET) is not indicated for routine local tumor staging, it seems to have better performance than conventional morphological imaging in LN staging and for all PC patients with suspected distant