Small-cell lung cancer is an extremely chemo-sensitive disease; the addition of immunotherapy to chemotherapy has demonstrated a slight clinical benefit in pivotal trials, even with a statistically ...significant difference in terms of survival outcomes when compared to chemotherapy alone. In this scenario, the role of radiotherapy as a consolidation treatment in thoracic disease or as a prophylactic therapy in the brain should be clarified. In addition, due to the frailty and the poor prognostic characteristics of these patients, the need for predictive biomarkers that could support the use of immunotherapy is crucial. PD-L1 and TMB are not actually considered definitive biomarkers due to the heterogeneity of results in the literature. A new molecular classification of small-cell lung cancer based on the expression of key transcription factors seems to clarify the disease behavior, but the knowledge of this molecular subtype is still insufficient and the application in clinical practice far from reality; this classification could lead to a better understanding of SCLC disease and could provide the right direction for more personalized treatment. The aim of this review is to investigate the current knowledge in this field, evaluating whether there are predictive biomarkers and clinical patient characteristics that could help us to identify those patients who are more likely to respond to immunotherapy.
Abstract Objectives Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC ...treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials. Materials and Methods We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3–8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival). Results Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test ( p ≤ 0.0001 for CSS and OS). Conclusion The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB).
Purpose
The purpose of this study was to assess prospectively the efficacy and safety of stereotactic body radiation therapy (SBRT) for adrenal gland metastasis, with a focus on the assessment of the ...irradiated subjects’ endocrinological function.
Materials and methods
A total of 36 patients were enrolled from 2017 to 2020 in this prospective phase II trial. Patients were treated with Linac-based SBRT, with a dose of 45 Gy in 3 consecutive fractions. Primary end-point was local control (LC) of the treated lesions and secondary end-points included evaluation of acute and late toxicity, progression free survival (PFS), overall survival (OS) and the impact on the hormonal production of adrenal glands.
Results
With a median follow-up of 9.5 months, LC rates at 1 and 2 years were 94.7% and 88.4%, respectively. Rates of PFS at 1 and 2 years were 50.5% and 29.8%, with a median PFS of 14.7 months. Rates of OS at 1 and 2 years were 62.9% and 44.1%. At univariate analysis, oligorecurrence was associated with better OS compared to oligoprogressive or synchronous metastatic disease. No grade 3 or greater toxicities were registered and only a minority of patients (22.2%) reported mild treatment-related side effects. Hormonal and electrolytes production was assessed before and after treatment, showing only a slight and transient variation within the reference ranges.
Conclusion
SBRT on adrenal metastases has been confirmed to be a feasible and effective treatment. With an excellent disease control and the preservation of the endocrine function, SBRT with ablative dose can be considered a viable alternative to more invasive approaches.
Purpose
The study aim was to compare the disease control in two groups of patients affected by liver metastases from CRC treated with microwave ablation (MWA) or stereotactic body radiation therapy ...(SBRT).
Methods
We extracted data of patients treated between 2009 and 2016. Inclusion criteria were: (1) maximum diameter of the liver lesions less than 4 cm; (2) no more than three liver lesions; (3) no evidence of progressive or untreated gross disease outside the liver; (4) adequate liver function; (5) no concurrent chemotherapy; (6) minimum age of 18. Tumour response was classified according to EORTC-RECIST criteria. Aim of the present study was to evaluate freedom from local progression (FFLP). To reduce indication bias, an inverse probability of treatment weighting was used to estimate treatment effect.
Results
A total of 135 patients with 214 lesions were included in the analysis. Median follow-up time was 24.5 months (range 2.4–95.8). The 1-year freedom from local progression (FFLP) was 88% (95%CI 80–92). In the SBRT group, FFLP was statistically longer than MWA group (
p
= 0.0214); the 1-year FFLP was 91% (95% CI 81–95) in SBRT group and 84% (95% CI 0.72–0.91) in MWA group. Patients treated with SBRT showed a reduce risk of local relapse compared to MWA (adjusted HR 0.31; 95%CI 0.13–0.70,
p
= 0.005). As expected, analogous result obtained in the inverse probability weighting analysis (HR 0.38; 95%CI 0.18–0.80;
p
= 0.011).
Conclusion
In conclusion, there seems to be an advantage of SBRT compared to MWA in treating CRC liver metastases, particularly for lesions bigger than 30 mm
To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer.
82 patients with 1-3 inoperable metastases confined to one organ ...(liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity.
Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with ≥ 60 Gy (n = 58) and those irradiated with <60 Gy (n = 52) was statistically significant, with a 1, 2 and 3 yrs LC of 97%,92% and 83% for the higher dose, compared to 85%,70% and 70% for the lower dose (p < 0.04). Median OS was 32 months. Actuarial OS rate at 1, 2 and 3 yrs was 85%,65% and 43%. Univariate analysis showed a correlation only between OS and cumulative GTV > 3 cm (p < 0.02). Median PFS was 14 months, with a PFS rate of 56% at 1 yr and 40% at 2-3 yrs, without correlation with the site and prescription dose (p < 0.48 and p < 0.56). No patients experienced radiation-induced liver disease or grade >3 toxicity.
SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments.
•No standard therapy is available for progressing malignant pleural mesothelioma (MPM).•Oligo-progression may occur in selected MPM patients.•In oligo-progressive MPM, high-dose focal radiotherapy ...(FRT) is feasible and safe.•FRT may allow delay of further systemic therapies.
No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM.
In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT, <5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy).
From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9–7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs >1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED > 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported.
FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.
To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT), realised with RapidArc and RapidPlan methods (RA_RP) for neoadjuvant ...radiotherapy in locally advanced oesophagal cancer.
Twenty patients were retrospectively planned for IMPT (with two fields, (IMPT_2F) or with three fields (IMPT_3F)) and RA_RP and the results were compared according to dose-volume metrics. Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the lungs. For the cardiac structures, the relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated.
Both the RA_RP and IMPT approached allowed to achieve the required coverage for the gross tumour volume, (GTV) and the clinical and the planning target volumes, CTV and PTV (V
> 98 for CTV and GTV and V
> 95 for the PTV)). The conformity index resulted in 0.88 ± 0.01, 0.89 ± 0.02 and 0.89 ± 0.02 for RA_RP, IMPT_2F and IMPT_3F respectively. With the same order, the homogeneity index for the PTV resulted in 5.6 ± 0.6%, 4.4 ± 0.9% and 4.5 ± 0.8%. Concerning the organs at risk, the IMPT plans showed a systematic and statistically significant incremental sparing when compared to RA_RP, especially for the heart. The mean dose to the combined lungs was 8.6 ± 2.9 Gy for RA_RP, 3.2 ± 1.5 Gy and 2.9 ± 1.2 Gy for IMPT_2F and IMPT_3F. The mean dose to the whole heart resulted to 9.9 ± 1.9 Gy for RA_RP compared to 3.7 ± 1.3 Gy or 4.0 ± 1.4 Gy for IMPT_2F or IMPT_3F; the mean dose to the left ventricle resulted to 6.5 ± 1.6 Gy, 1.9 ± 1.5 Gy, 1.9 ± 1.6 Gy respectively. Similar sparing effects were observed for the liver, the kidneys, the stomach, the spleen and the bowels. The EAR per 10,000 patients-years of secondary cancer induction resulted in 19.2 ± 5.7 for RA_RP and 6.1 ± 2.7 for IMPT_2F or 5.7 ± 2.4 for IMPT_3F. The RR for the left ventricle resulted in 1.5 ± 0.1 for RA_RP and 1.1 ± 0.1 for both IMPT sets. For the coronaries, the RR resulted in 1.6 ± 0.4 for RA_RP and 1.2 ± 0.3 for protons.
With regard to cancer of the oesophagogastric junction type I and II, the use of intensity-modulated proton therapy seems to have a clear advantage over VMAT. In particular, the reduction of the heart and abdominal structures dose could result in an optimised side effect profile. Furthermore, reduced risk of secondary neoplasia in the lung can be expected in long-term survivors and would be a great gain for cured patients.
Lymph nodes are common sites of oligometastases for several primaries. Stereotactic body radiation therapy (SBRT) represents an effective treatment but no consensus exists regarding dose and ...fractionation. Aim of this trial was to evaluate safety and efficacy of high-dose SBRT. We included patients with 1 to 3 lymph node metastases. Primary end-point was safety, while secondary end-points were in-field local control (LC), out-field lymph nodal progression free survival (LPFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). 64 lesions in 52 patients were treated from 2015 to 2019. Most common primary tumor was genitourinary cancer (75%), in particular prostate cancer (65.4%). With a median follow-up of 24.4 months (range 3–49), treatment was very well tolerated, with only 4 (7.7%) patients reporting acute side effects, all classified as grade 1, in the form of pain, fatigue, nocturia and dysuria. No toxicity ≥ grade 2 were reported. Rates of LC at 1, 2 and 3 years were 97.9%, 82.1% and 82.1%. Male sex (HR 0.12, p value 0.014) was associated with improved LC. LPFS at 1, 2 and 3 years were 69.6%, 49.6% and 46.1%, respectively, and DMFS was 81.74%, 67.5% and 58.5%, respectively. Presence of lesions in other organs was correlated with inferior DMFS (HR 3.82, p = 0.042). PFS at 1, 2 and 3 years were 67.4%, 42.4% and 31.86%, respectively. OS at 1, 2 and 3 years were 97.3%, 94.2%, 84%, respectively and significantly correlated with in-field recurrence (HR 8.72, p = 0.000). Our prospective trial confirms safety and efficacy of SBRT in the management of lymph node metastases. Registered Clinical trial NCT02570399.
Introduction
Stereotactic Body Radiotherapy (SBRT) emerged as a valuable option in early to advanced-stage Hepatocellular Carcinoma (HCC) as defined by Barcelona Clinic Liver Cancer (BCLC) system. ...The aim of our study is to evaluate SBRT in HCC patients and to identify predictors of outcome and toxicity.
Materials and methods
A retrospective review of HCC patients treated at our Institution between November 2011 and December 2018 was carried out. SBRT was delivered in 3-10 fractions to a median Biologically Effective Dose (BED
10
) of 103 Gy
10
.
Results
SBRT was performed in 128 patients to 217 HCC localizations, accounting for 142 treatment courses. BCLC stage was A, B, C in, respectively, 40 (31%), 72 (56%) and 16 (13%) patients. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) at 2 years were, respectively: 78%, 15% and 58%. LC was influenced by BED10 > 120 Gy
10
(Hazard Ratio, HR: 0.08, 95% CI 0.01–0.59;
p
= 0.013) and size ≥ 3 cm (HR: 2.71, 95% CI 1.10–6.66;
p
= 0.03). BCLC stage was correlated to PFS (median 14 vs 12 vs 5 months,
p
= 0.012). In BCLC stage A-B disease (
n
= 112), LC was associated with improved survival (median 30 months vs not reached,
p
= 0.036). Acute and late toxicity rate was 26% (
n
= 37) and 8% (
n
= 11). Patients with BCLC B-C stage disease showed increased acute toxicity (HR: 2.9, 95% CI 1.10–7.65;
p
= 0.032).
Conclusion
Delivery of ablative doses > 120 Gy
10
and tumor size are determinants of LC. Prolonged PFS and improved OS can be obtained in BCLC A-B patients. Grade 3 liver dysfunction is infrequent.
To test feasibility and safety of clinical usage of Flattening Filter Free (FFF) beams for delivering ablative stereotactic body radiation therapy (SBRT) doses to various tumor sites, by means of ...Varian TrueBeam™ (Varian Medical Systems).
Seventy patients were treated with SBRT and FFF: 51 lesions were in the thorax (48 patients),10 in the liver, 9 in isolated abdominal lymph node, adrenal gland or pancreas. Doses ranged from 32 to 75 Gy, depending on the anatomical site and the volume of the lesion to irradiate. Lung lesions were treated with cumulative doses of 32 or 48 Gy, delivered in 4 consecutive fractions. The liver patients were treated in 3 fractions with total dose of 75 Gy. The isolated lymph nodes were irradiated in 6 fractions with doses of 45 Gy. The inclusion criteria were the presence of isolated node, or few lymph nodes in the same lymph node region, in absence of other active sites of cancer disease before the SBRT treatment.
All 70 patients completed the treatment. The minimum follow-up was 3 months. Six cases of acute toxicities were recorded (2 Grade2 and 2 Grade3 in lung and 2 Grade2 in abdomen). No patient experienced acute toxicity greater than Grade3. No other types or grades of toxicities were observed at clinical evaluation visits.
This study showed that, with respect to acute toxicity, SBRT with FFF beams showed to be a feasible technique in 70 consecutive patients with various primary and metastatic lesions in the body.
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