Rolando Maria D’Angelillo

Surgery for patients with persistent pathological N2 IIIA stage in non-small-cell lung cancer after induction radio-chemotherapy: the microscopic seed of doubt §

OBJECTIVE The surgical treatment of residual N2 disease following induction radio-chemotherapy (IT) for locally advanced cIIIA-N2 non-small-cell lung cancer (NSCLC) is still debated. The long-term results after resection in a pN2 series are at the focus of this study. METHODS From January 1992 to December 2008, 161 consecutive pathologically proven Stage IIIA-N2 NSCLC patients underwent IT. Among these, 40 pN2s were included in this retrospective analysis. The associations between the mortality and the disease-free status with potential risk factors were explored by means of the Kaplan-Meier and Cox regression analysis. RESULTS Mean age and male/female ratio were 58.7 ± 9.7 years and 36/4, respectively. Twelve patients (30%) showed a clinical partial response and 28 (70%) showed stable disease. There was one (3%) perioperative death and four (10%) major complications. In the total group, the 3- and 5-year survival rates were 24.2% and 19.3%, respectively. The Cox regression analysis suggested that the macroscopic pN2 status proved to be a negative prognostic factor (hazard ratio (HR)=2.8, confidence interval (CI) 95%: 1.1-7.3; p=0.04). The recurrence rate flattened at 30.8% at the 3rd year. Furthermore, the bilobectomy-pneumonectomy group had a risk of relapse 6.9 times higher than the lobectomy group (CI 95%: 2.5-18.8; p < 0.001). CONCLUSIONS The persistence of disease at the N2 level after IT and surgery for cIIIa-N2 NSCLC does not exclude favorable outcome after resection, in particular in those patients with minor residual disease.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

Background:The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods:Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results:About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions:Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

SBRT: A viable option for treating adrenal gland metastases

The management strategy of adrenal metastases depends on different clinical situations. Adrenal metastasectomy in selected patients with isolated adrenal metastases is considered the treatment of choice, showing prolonged survival compared to chemotherapy alone. More recently, Stereotactic Body Radiation Therapy (SBRT) has emerged as an alternative local ablative treatment modality although limited data are available on the use of SBRT in treating adrenal gland metastases. Preliminary results are, however, encouraging, especially in selected patients with oligometastatic disease. We herewith review and discuss the potential role of SBRT as a local ablative treatment modality for adrenal metastases.

A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective

OBJECTIVE To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. METHODS AND MATERIALS An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). RESULTS With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1 ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. CONCLUSIONS ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.

Pulmonary rehabilitation following radical chemo-radiation in locally advanced non surgical NSCLC: Preliminary evidences

pulmonary rehabilitation (PR) has been fully included in the trategy for treatment of lung cancer [1]. Evidences from ranomised controlled trials (RCTs) are scarce and limited to the ost-surgical setting [2] but a systematic review on the topic as recently concluded that “(rehabilitative) interventions preperatively or post-cancer treatment are associated with positive enefits on exercise capacity, symptoms and some domains of RQoL” [3]. We have a long-standing interest in this approach [4–6] nd the positive results in our everyday clinical practice, based n extensive multidisciplinary cooperation, have prompted us to xplore its further application beyond the strictly “peri-surgical” etting. We have therefore offered to patients with locally advanced SCLC who are not suitable for surgical treatment an inpatient Pulonary Rehabilitation protocol (iPR), comprehensively described n [4] and summarised below. According to oncological guideines, these patients undergo concurrent chemo-radiation (CTRT) dministered with radical intent where pulmonary toxicity is one f the most important adverse effect limiting the delivered radition dose (and plausibly the overall cure rate). We report here ur preliminary findings, in a setting not matched with a control roup, on the feasibility and efficacy of this approach. Following nformed consent and communication to the local ethical comittee, according to national guidelines and regulations the iPR s routinely prescribed and performed on the basis of the pulonary functionality of patients. Following the chemo-radiation

Erlotinib and Concurrent Chemoradiation in Pretreated NSCLC Patients: Radiobiological Basis and Clinical Results

Aims. To establish feasibility of the combination of Erlotinib and concurrent chemoradiation in pre-treated patients with locally advanced or metastatic NSCLC. Materials and Methods. Data regarding 60 consecutive patients with NSCLC previously treated with chemotherapy alone were prospectically collected. All patients started Erlotinib concurrently with chemotherapy and radiation delivered to primary tumor. These data were retrospectively analyzed (observational study). Feasibility and toxicity were the primary endpoints, with response rate and progression being the secondary ones, while survival data are reported just as exploratory analysis. The EGFR mutational status was recorded in 32% of cases and it was always wild type. Results. Compliance to the combination protocol was good. Grade 3-4 esophagitis and acute lung toxicity occurred in 2% and 8% of patients, respectively. No progressive disease was recorded in the majority of cases (65%). Median OS and PFS were 23.3 and 4.7 months, respectively. Patients not responding to chemotherapy administered prior to chemoradiation achieved an objective response rate of 53.3% and complete response in 13.3% of cases. Conclusions. The addition of Erlotinib to chemoradiation in inoperable NSCLCs is feasible with interesting efficacy profile. These preliminary results warrant further investigation in patients with locally advanced nonmetastatic NSCLC with EGFR mutations.

Radiotherapy in palliative treatment of metastatic NSCLC: not all one and the same

This is not the first editorial on palliative radiotherapy in metastatic NSCLC. Moreover, this is not the first editorial which underlines the relationship between radiotherapy dose/fractionation and patient prognosis. So, why another one? And why another one now?

Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.

Multidisciplinary teams for the proper management of patients with genitourinary tumors: When topics set scientific societies’ agenda

Introduction: The multidisciplinary management of oncologic patients is identified as the bottom line element of quality in tumor care. Methods: In 2015, 7 Italian scientific societies representing the specialists involved in the diagnosis and treatment of genitourinary tumors joined efforts in the Italian uro-oncologic multidisciplinary teams (MDTs) project. The aims were to promote the reorganization of genitourinary cancer care, switching to a multidisciplinary approach, reach a consensus on the core elements for the setup of MDTs in genitourinary oncology, and support health policy makers and managers in remodeling of the assistance and care of uro-oncologic patients on a national level. Results: The first activity was the setup of 5 working groups, given the task of exploring selected topics: general principles, organization of MDTs, minimal requirements, economic evaluation, and relations with authorities. The groups participated in the writing of a document that was approved by the scientific societies and published on their web sites. Moreover, a few items summarizing the extensive document were approved in the first MDT Consensus Conference held in Milan in December 2015. Conclusions: The experience of this initial phase led to the opening of the team to other professionals and societies, in line with a correct management of patients with genitourinary tumors, which need a multidisciplinary as well as a multiprofessional approach with emerging techniques and procedures, and with a new project work package on genitourinary paths of care and indicators.

Implementation of a voluntary deep inspiration breath hold technique (vDIBH) using BrainLab ExacTrac infrared optical tracking system

Background Voluntary deep inspiration breath hold technique (vDIBH) is considered as the key to achieving the widest cardiac sparing in whole breast irradiation. Several techniques have been implemented to achieve a reproducible, fast and friendly treatment. The aim of the present study is to implement vDIBH using the ExacTrac (BrainLAB AG, Germany) monitoring system. Methods Women with left-sided breast cancer, younger than 50 years or with cardiac disease, underwent whole breast RT with vDIBH using the ExacTrac (BrainLAB AG, Germany) monitoring system. Simulations were performed with patients positioned supine on a breast board with both arms raised above the head. Five optical markers were placed on the skin around the border of the left breast gland and their position was referenced with ink marking. Each patient received a training session to find the individual deep inspiration level. Finally, a vDIBH CT was taken. All patients were also studied in free breathing (FB) in order to compare the dose distribution for PTV, heart and left anterior descending coronary artery (LAD). Pre-treatment verification was carried out through the ExacTrac (BrainLAB AG, Germany) system and verified with electronic portal imaging (EPI). Moreover, daily real time EPIs in during modality (captured during the beam delivery) were taken in order to check the reproducibility. Results 34 patients have been evaluated and 30 were eligible for vDIBH. Most patients showed small setup errors during the treatment course of below 5 mm in 94.9% of the recorded fields. Mean Displacement was less in cranio-caudal direction. Mean intra-fraction displacement was below 3 mm in all directions. vDIBH plans provided better cardiac dosimetry. Conclusions vDIBH technique using ExacTrac (BrainLAB AG, Germany) monitoring system was applied with good reproducibility.