Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

Preliminary Results of a Randomized Study on Postmenopausal Women With Early Stage Breast Cancer: Adjuvant Hypofractionated Whole Breast Irradiation Versus Accelerated Partial Breast Irradiation (HYPAB Trial).

BACKGROUND: The purpose of this study was to report preliminary data of a randomized phase III trial comparing hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) using volumetric modulated arc therapy (VMAT). MATERIAL AND METHODS: The HYPAB trial enrolled postmenopausal women with biopsy-proven infiltrating breast cancer, clinically negative axilla, single T1 to T2 tumors, who were treated with breast-conserving surgery. Patients were randomized 1:1 after surgery to HWBI (40.5 Gy whole breast, 48.0 Gy to surgical bed, 15 fractions over 3 weeks) or APBI (30 Gy delivered in 5 fractions of 6 Gy given on alternate days on the surgical bed). Cosmetic outcome was the primary end point of the study. RESULTS: A total of 172 patients were enrolled. After a median follow-up of 36 months, 5 local failures and 3 locoregional failures were recorded, with no difference between the 2 treatment arms. Use of HWBI as compared with APBI was significantly correlated with increased incidence of overall (62% vs. 14%; P < .001) and grade 2 (18% vs. 1%; P < .001) acute skin toxicity. APBI was correlated with a lower incidence of overall late toxicity as compared with HWBI (18% vs. 41%; P = .001), but no significant difference was found in term of occurrence of grade 2 events (1% vs. 4%; P = NS). At comparative assessment between baseline and post-radiotherapy evaluation, impairment in cosmetic outcome was reported in 19 (11%) patients. Owing to premature closure of the study, no per-protocol comparison between the treatment arms was performed. CONCLUSION: APBI with the VMAT technique is safe and feasible, with lower acute toxicity when compared with HWBI.

Stereotactic Radiotherapy for Ultra-Central Lung Oligometastases in Non-Small-Cell Lung Cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated. METHODS: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence. RESULTS: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75-132) Gy10. Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy10 was correlated to superior LC (p = 0.02), PFS (p = 0.036), and OS (p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity. CONCLUSIONS: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur.

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment's intensification?

BACKGROUND AND PURPOSE: Lymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors. MATERIALS AND METHODS: We included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI). RESULTS: 418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%. CONCLUSION: With the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.

Reirradiation of pulmonary artery intimal sarcoma: A case report.

We report here the case of a patient with 4 years long-term survival after treatment with surgery, chemotherapy, and radiotherapy with good local control. This case highlights the possible role of radiation therapy in this tumor.

Individualized treatment of head neck squamous cell carcinoma patients aged 70 or older with radiotherapy alone or associated to cisplatin or cetuximab: impact of weekly radiation dose on loco-regional control.

The purpose of this study is to evaluate if, in elderly HNC patients, loco-regional control (LRC) is influenced by average weekly radiation dose (AWD). From 2009 to 2017, 150 consecutive HNC elderly patients were analyzed. AWD was calculated by dividing total dose in Gray by overall treatment time in weeks. Patients were divided in 2 groups: Group 1 (70-75 years) and Group 2 (> 75 years). Primary endpoint was LRC; secondary endpoints were overall survival (OS) and compliance to treatment. The median age was 76 years (range 70-92), the distribution of patients by age was 72 and 78 patients in Group 1 and in Group 2, respectively; overall median follow-up was 23 months. Optimal cut-off of AWD for LRC was 9.236 (p = 0.018). Median OS was 73 months. In univariate survival analysis low PS (p = 0.005), T3-T4 (p = 0.021), Stage III-IV (p = 0.046) and AWDLow (< 9.236) (p = 0.018) were significantly associated with lower LRC; low PS (p < 0.001) and Group 2 (p = 0.006) were also associated with lower OS. Considering patients treated with radiotherapy alone AWDLow was significantly associated with lower LRC (p = 0.04) whereas among patient treated with chemoradiotherapy AWD did not affected LRC (p = 0.18). The multivariate analysis confirmed the significant value of PS for the prediction of LRC and OS (p = 0.035 and p < 0.001, respectively). In elderly patients an AWD of > 9.236 Gy was found to be beneficial for RT alone regimen. When radiotherapy alone is indicated in elderly patients an effort should be made to maintain an increased AWD in order to improve LRC.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report.

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 - PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.