Radiosurgery and fractionated stereotactic radiotherapy in oligometastatic/oligoprogressive non-small cell lung cancer patients: Results of a multi-institutional series of 198 patients treated with "curative" intent.

OBJECTIVES: stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are a therapeutic option for Oligometastatic/Oligoprogressive (OM/OP) NSCLC. This retrospective multicentre analysis aims to analyse clinical outcomes and treatment related toxicity of patients treated to all sites of know disease with SRS and/or FSRT for OM/OP NSCLC in 8 Italian radiation oncology centres. MATERIALS AND METHODS: From January 2016 to January 2017 198 OM/OP NSCLC patients (pts) were treated in 8 Centres. Inclusion criteria were as follows: 1-5 lesions at onset or after previous systemic treatment; Pts must have all metastatic lesions treated. Endpoints analysed were local progression free survival (LPFS); out-of-field recurrence free survival (OFPS); progression free survival (PFS); overall survival (OS). Time to New systemic Therapy free survival (TNT) and toxicity were also analysed. RESULTS: At the time of radiotherapy, 119 pts (60 %) were treated for a single lesion, 49 (25 %) for 2 lesions, 30 (15 %) for 3-5 metastases. Total number of lesions treated was 333: 204 brain, 68 lung, 24 bone, 16 nodal, 12 adrenal, 8 liver and 1 soft tissue. 83/198 pts (41.8 %) had the primary tumour controlled at the time of the SRT. After a median follow-up of 18 months, median OS and PFS were 29.6 months and 10.6 months, respectively. One year LPFS and OPFS were 90 % and 47 %, respectively. Median TNT was 10 months. At univariate analysis factors associated with better OS were PS 0-1; controlled primary tumour, 1-2 lesions; extracranial metastasis. Multivariate analysis confirmed number of lesions <3 and extracranial metastasis to be related with better survival (Relative Risk 0.4 and 0.41, respectively). Two cases of death possibly related to brain radionecrosis were observed. CONCLUSION: OM/OP NSCLC pts treated with an ablative SRT to all metastatic sites have fair outcomes with acceptable toxicity. Better results might be achieved in case of low disease burden and extracranial possibly when primary tumour is controlled.

Radiotherapy for oligometastatic cancer: a survey among radiation oncologists of Lombardy (AIRO-Lombardy), Italy.

AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.

Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

Set-up errors in head and neck cancer patients treated with intensity modulated radiation therapy: Quantitative comparison between three-dimensional cone-beam CT and two-dimensional kilovoltage images.

OBJECTIVES: To compare the patient set-up error detection capabilities of three-dimensional cone beam computed tomography (3D-CBCT) and two-dimensional orthogonal kilovoltage (2D-kV) techniques. METHODS: 3D-CBCT and 2D-kV projections were acquired on 29 head-and-neck (H&N) patients undergoing Intensity Modulated Radiotherapy (IMRT) on the first day of treatment (time 0) and after the delivery of 40 Gy and 50 Gy. Set-up correction vectors were analyzed after fully automatic image registration as well as after revision by radiation oncologists. The dosimetric effects of the different sensitivities of the two image guidance techniques were assessed. RESULTS: A statistically significant correlation among detected set-up deviations by the two techniques was found along anatomical axes (0.60 < ρ < 0.72, p < 0.0001); no correlation was found for table rotation (p = 0.41). No evidence of statistically significant differences between the indications provided along the course of the treatment was found; this was also the case when full automatic versus manually refined correction vectors were compared. The dosimetric effects analysis revealed slight statistically significant differences in the median values of the maximum relative dose to mandible, spinal cord and its 5 mm Planning Organ at Risk Volume (0.95%, 0.6% and 2.45%, respectively), with higher values (p < 0.01) observed when 2D-kV corrections were applied. CONCLUSION: A similar sensitivity to linear set-up errors was observed for 2D-kV and 3D-CBCT image guidance techniques in our H&N patient cohort. Higher rotational deviations around the table vertical axis were detected by the 3D-CBCT with respect to the 2D-kV method, leading to a consistent better sparing of organs at risk.

Contouring of the Pharyngeal Superior Constrictor Muscle (PSCM). A cooperative study of the Italian Association of Radiation Oncology (AIRO) Head and Neck Group.

BACKGROUND AND PURPOSE: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images. MATERIALS AND METHODS: Three sets of treatment planning CT and their corresponding MR images were selected. Contouring of the PSCM was performed using both a literature-based method, derived from literature review, and an optimized method, derived from Magnetic Resonance (MR) images thus obtaining "literature-based" and "optimized" contours. Each operator contoured the PSCM on CT scans according to both methods for three times in three different days. Inter- and intra-operator variability and adherence to a contour obtained from MR images (named "MR-derived" contour) were analyzed. RESULTS: Thirty-four operators participated and 612 contours were obtained. Both intra- and inter-operator variability and adherence to the "MR-derived" contour were significantly different between the two methods (p⩽0.05). The "optimized" method showed a lower intra- and inter-operator variability and a higher adherence to the "MR-derived" contour. CONCLUSIONS: The "optimized" method ameliorates both operator-related variability and adherence with MR images.

Outcomes of radiation therapy for T1 glottic carcinoma from an Italian regional series with doses ranging from 60 to 66 Gy.

AIMS AND BACKGROUND: Radiotherapy has remarkable success rates for the cure of patients affected by glottic carcinoma; local control rates are similar to surgery with lower morbidity and better functional results. Our aim was to determine local-regional control rates, overall survival, second cancer incidence, acute-late toxicity and prognostic factors in our series of T1 glottic cancer patients with radiation doses of 60 to 66 Gy. Functional results were not sufficient for statistical analysis. METHODS AND STUDY DESIGN: A retrospective study was carried out of all T1N0 glottic carcinomas treated with radiation therapy between 1996 and 2006. To be eligible, patients had to have newly diagnosed cancer and had to be treated with a curative intent by radiation therapy alone. Ninety-eight patients satisfied the eligibility requirements: 85 patients had T1a disease; 13 patients were staged as T1b. Treatment was performed for all cases with a 6 megavoltage linear accelerator. The total dose prescribed varied from 60 to 66 Gy: 2 Gy/fraction, 1 fraction/day, 5 fractions/week. During treatment, a weekly clinical evaluation was performed; endoscopic examination was performed once every two weeks. After the treatment, a clinical, endoscopic and radiological follow-up was performed every three months for the first two years, every 6 months till the fifth year, and then once a year. RESULTS: With a median follow-up of 41.5 months (range, 10-132; mean, 56.8), we registered 12 cases of local failures; 8 of them were successfully treated with salvage surgery (median time to relapse, 3-48 months). The local relapse rate was 12.2%, and disease-specific survival, taking into account salvage surgery, was 6%. Thirty-four deaths were registered: 2 for local progression, 2 for distant metastasis, 4 for a new primary cancer, and 26 for non-neoplastic causes. Five- and 10-year overall survival were respectively 85.8% and 69.4%. Four cases of lung cancer were detected in the upper aerodigestive tract in our series. In terms of acute-late toxicity, no grade 3-4 dermatitis, dysphagia or hoarseness occurred. Mild dermatitis and arythenoid edema were the most common causes of toxicity. Only one patient did not complete the treatment (60 Gy instead of the planned 66 Gy). CONCLUSIONS: Our series confirmed the primary role of radiation therapy for the cure of T1N0 glottic cancer. Outcomes were good in terms of local-regional control as well as overall toxicity. Radiation therapy can be offered to T1 glottic cancer patients as a valid alternative to surgery, with high rates of functional preservation.