Clinical implications of the family history in patients with lung cancer: a systematic review of the literature and a new cross-sectional/prospective study design (FAHIC: lung).

Compared to other malignancies, few studies have investigated the role of family history of cancer (FHC) in patients with lung cancer, yielding largely heterogeneous results. We performed a systematic literature review in accordance with PRISMA guidelines, searching the PubMed and Scopus databases from their inception to November 25, 2023, to identify studies reporting on the role of FHC in patients with lung cancer. A total of 53 articles were included, most with a retrospective design and encompassing a variety of geographical areas and ethnicities.Thirty studies (56.6%) assessed patients with non-small cell lung cancer (NSCLC), while 17 studies (32.1%) assessed patients with mixed histologies. Overall, the rates of FHC ranged from 8.3 to 68.9%, and the rates of family history of lung cancer ranged from 2 to 46.8%. Twenty-seven studies investigated FHC as a potential risk factor for lung cancer, with more than half reporting an increased risk for subjects with FHC. Five studies reported on the potential role of FHC in determining clinical outcomes, and twelve studies examined the relationship between FHC and germline mutations. Notably, only one study reported a significantly increased rate of germline mutations, including ATM, BRCA2, and TP53, for patients with a family history of lung cancer compared to those without, but both groups had a low prevalence of mutations (< 1%).The FAHIC-Lung (NCT06196424) is the first cross-sectional/prospective study specifically developed to identify FHC patterns and within-family clusters of other risk factors, including smoking, to guide patients with NSCLC to systematic genetic counseling. Acknowledging the largely heterogeneous results of our systematic review and considering the clinical implications of detecting pathogenic germline variants (PGVs), the FAHIC-lung study aims to identify patients potentially enriched with PGVs/likely PGVs to direct them to germline screening outside of the research setting.

The burden of epilepsy on long-term outcome of genetic developmental and epileptic encephalopathies: A single tertiary center longitudinal retrospective cohort study.

BACKGROUND: This retrospective cohort analysis highlighted neurodevelopmental outcome predictors of genetic developmental and epileptic encephalopathies (DEE). PATIENTS AND METHODS: Patients' demographic, clinical and molecular genetics data were collected. All patients underwent clinical, developmental, and neuropsychological assessments. RESULTS: We recruited 100 participants (53 males, 47 females) with a mean follow-up lasting 10.46 ± 8.37 years. Age at epilepsy-onset was predictive of poor adaptive and cognitive functions (VABS-II score, r = 0.350, p = 0.001; BRIEF control subscale, r = -0.253; p = 0.031). Duration of epilepsy correlated negatively with IQ (r = -0.234, p = 0.019) and VABS-II score (r = -0.367, p = 0.001). Correlations were found between delayed/lacking EEG maturation/organization and IQ (r = 0.587, p = 0.001), VABS-II score (r = 0.658, p = 0.001), BRIEF-MI and BRIEF-GEC scores (r = -0.375, p = 0.001; r = -0.236, p = 0.033), ASEBA anxiety (r = -0.220, p = 0.047) and ADHD (r = -0.233, p = 0.035) scores. The number of antiseizure medications (ASMs) correlated with IQ (r = -0.414, p = 0.001), VABS-II (r = -0.496, p = 0.001), and BRIEF-MI (r = 0.294, p = 0.012) scores; while age at the beginning of therapy with ASEBA anxiety score (r = 0.272, p = 0.013). The occurrence of status epilepticus was associated with worse adaptive performances. The linear regression analysis model showed that delayed/lacking EEG maturation/organization had a significant influence on the IQ (R2 = 0.252, p < 0.001) and the BRIEF-GEC variability (R2 = 0.042, p = 0.036). The delayed/lacking EEG maturation/organization and the duration of epilepsy also had a significant influence on the VABS-II score (R2 = 0.455, p = 0.005). CONCLUSIONS: Age at seizure-onset, EEG maturation/organization, duration of epilepsy, occurrence of status epilepticus, age at the introduction and number of ASMs used are reliable predictors of long-term outcomes in patients with genetic DEE.

Concurrent Use of Abemaciclib and Radiotherapy in Metastatic Breast Cancer Patients: A Single-Center Experience.

INTRODUCTION: There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. METHODS: Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. RESULTS: Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p < 0.0001). CONCLUSION: Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

Artificial intelligence applied to image-guided radiation therapy (IGRT): a systematic review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

INTRODUCTION: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered. RESULTS: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques. DISCUSSION: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies.

Are you planning to be a radiation oncologist? A survey by the young group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

BACKGROUND AND PURPOSE: The Young Section of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO) circulated an online questionnaire survey among residents currently enrolled within Italian radiotherapy residency schools to investigate the profiles, motivations, knowledge of the radiotherapy discipline, organizations and the needs of younger members. MATERIALS AND METHODS: The survey was developed by the yAIRO steering committee and included questions about the demographic characteristics of the residents (Profile A), the background of their clinical experience during the school of medicine and national residency admission test performance (Profile B) and the residents' knowledge of the scientific associations active in the field of radiotherapy (Profile C). RESULTS: Out of 400 residents actually in training, 134 responded to the questionnaire (response rate 33.5%). According to most of the residents, radiotherapy was not adequately studied during the medical school (n. 95; 71%) and an Internship in Radiotherapy was not mandatory (n. 99; 74%). Only a minority of the residents had chosen to complete a master's degree thesis in radiotherapy (n. 12; 9%). A low percentage of the residents stated that they were aware of the Italian Association of Radiotherapy and Clinical Oncology (AIRO), its young section (yAIRO) and the European Society for Radiotherapy and Oncology (ESTRO) when they were in School of Medicine (respectively, 11%, 7% and 13%). CONCLUSIONS: The results of the survey require a profound reflection on the current teaching methods of Radiation Oncology in our country, highlighting the need for a better integration in the framework of the School of Medicine core curriculum.

How I Treat Localized Soft Tissue Sarcomas: Update on Diagnosis, Risk Stratification, and Treatment.

BACKGROUND: Adult-type soft tissue sarcomas (STSs) are rare tumors representing about 1% of all adult malignant tumors. Their extreme histological heterogeneity places them among the most challenging fields of diagnostic pathology. The variability of clinical and prognostic presentation between the various histotypes reflects the different management that should be followed on a case-by-case basis. These features make STSs the case in point of how important it is a centralized and multidisciplinary approach. SUMMARY: Surgery represents the mainstay in the treatment of localized STSs. Recently, more and more studies are making efforts to understand what the contribution of chemotherapy and radiotherapy with neoadjuvant and adjuvant intent may be both in unselected and selected histological subgroups. In fact, despite the improvement in overall survival seen in the past few years thanks to the adoption of a more radical surgical approach, mortality remains relatively high and the 5-year overall survival is around 65%. KEY MESSAGES: In this review, we comment upon the treatment of localized STSs of the extremity, trunk wall, and retroperitoneum and how surgery, radiotherapy, and chemotherapy can be integrated with each other and individually tailored. Nomograms can assist clinicians in this complex therapeutic decision-making process, through the identification of patients at higher risk of death or disease relapse.

TSC1 as a Novel Gene for Sleep-Related Hypermotor Epilepsy: A Child with a Mild Phenotype of Tuberous Sclerosis.

Sleep-related hypermotor epilepsy (SHE) is a rare syndrome that presents with hyperkinetic asymmetric tonic/dystonic seizures with vegetative signs, vocalization, and emotional facial expression, mainly during light non-rapid eye movement sleep stages. The role of various genes (CHRNA4, CHRNB2, CHRNA2, KCNT1, DEPDC5, NPRL2, NPRL3, and PRIMA1) has previously been reported, though genetic etiology is assessed in less than 10% of cases. We report the case of a 5-year-old female carrying the TSC1 variant c.843del p.(Ser282Glnfs*36) who presented with a mild phenotype of tuberous sclerosis, including carbamazepine-responsive SHE, normal neurocognitive functioning, hypomelanotic macules, no abnormalities outside the central nervous system, and tubers at neuroimaging. The presented case extends the list of SHE-related genes to include TSC1, thus suggesting a central pathogenic role of mammalian target of rapamycin (mTOR) cascade dysfunction in SHE and introducing a possible use of mTOR inhibitors in this epileptic syndrome.

ESTRO vision 2030: the young Italian Association of Radiotherapy and Clinical Oncology (yAIRO) commitment statement.

The aim of this document is to share the action plan from the young Italian Association of Radiotherapy and Clinical Oncology (yAIRO). We believe it is important to enhance a constructive dialog between societies. The hope is to offer to young radiation oncologists a wealth of opportunities to refine their skills and gain access to the latest developments, according to a shared European vision.

Repeated courses of radiation treatment in an HER2-positive breast cancer patient with diffuse brain metastases: A case report.

In human epidermal growth factor receptor 2 (HER2+) expressing breast cancer subtype, the incidence of brain metastases is common and patients often die due to uncontrolled cranial disease. This is a case report of a HER2+ breast cancer woman with diffuse brain metastases that experienced long survival and clinical benefit from multiple radiotherapy treatments and combined systemic therapy, without increased toxicity.

18F-choline PET/CT driven salvage radiotherapy in prostate cancer patients: up-date analysis with 5-year median follow-up.

PURPOSE: Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value < 0.5 ng/ml at relapse, while 60-66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. METHODS: Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. RESULTS: Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2-17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.4%) late acute genitourinary grade 3 toxicity. With a median follow-up of 63.5 months, 5 and 7-years relapse-free survival were 70% and 60.7%, respectively. CONCLUSION: With a median follow-up of 5 years the present study confirms that high-dose salvage radiotherapy to a biological target volume is feasible, with low rate of late toxicity and promising activity.

Pharmacology of Ranolazine versus Common Cardiovascular Drugs in Patients with Early Diastolic Dysfunction Induced by Anthracyclines or Nonanthracycline Chemotherapeutics: A Phase 2b Minitrial.

We have reported that anthracyclines and nonanthracycline chemotherapeutics caused diastolic dysfunction in cancer patients without cardiovascular risk factors. Diastolic dysfunction occurred as early as 1 week after the last chemotherapy cycle and manifested as impaired myocardial relaxation at echocardiography or persistent elevations of B-type natriuretic peptide (BNP) or troponin. The antianginal drug ranolazine shows cardiac relaxant effects that we considered of value to treat early diastolic dysfunction induced by cancer drugs; therefore, 24 low-risk patients with post-chemotherapy diastolic dysfunction were randomized (1:1) to ranolazine or the investigator's choice of common cardiovascular drugs, such as ß-blockers and/or angiotensin-converting enzyme inhibitors or loop diuretics (best standard therapy, BST). After 5 weeks, 12 of 12 patients on ranolazine recovered from diastolic dysfunction, whereas 3 of 12 patients on BST did not improve; however, adverse events (not serious) were apparently more frequent for ranolazine than for BST (4/12 vs. 1/12). Ranolazine did not lower blood pressure, whereas BST reduced systolic pressure and caused a trend toward a reduced diastolic pressure. Most patients at randomization showed tachycardia resulting from chemotherapy-related anemia. Hemoglobin recovery contributed to normalizing heart rate in these patients; however, some patients in the ranolazine arm developed tachycardia through chronotropic effects of high BNP levels and returned to a normal heart rate through the effects of ranolazine on decreasing BNP levels. This minitrial describes the potential effects of ranolazine on relieving chemotherapy-related diastolic dysfunction; however, clinical implications of these findings need to be characterized by studies with an adequate sample size. SIGNIFICANCE STATEMENT: The antianginal drug ranolazine causes cardiac relaxant effects that might relieve diastolic dysfunction. In a clinical pharmacology study, 24 patients were randomized (1:1) to receive ranolazine or common cardiovascular drugs to treat early diastolic dysfunction induced by anthracycline-based or nonanthracycline chemotherapy. Ranolazine relieved diastolic dysfunction in these patients. The safety profile of ranolazine in cancer patients is similar to that of the general population. Compared with common cardiovascular drugs, ranolazine relieved diastolic dysfunction without lowering blood pressure. The sample size of this study was nonetheless too small to permit considerations about the potential clinical value of ranolazine for oncologic patients with early diastolic dysfunction induced by anthracyclines or nonanthracycline chemotherapeutics. This information should be obtained by studies with an adequate sample size.

Concomitant radiotherapy and TKI in metastatic EGFR- or ALK-mutated non-small cell lung cancer: a multicentric analysis on behalf of AIRO lung cancer study group.

PURPOSE: To investigate the role of radiotherapy (RT) in the management of EGFR- or ALK-mutated metastatic non-small cell lung cancer (NSCLC) treated with TKI. MATERIALS AND METHODS: Clinical data of 106 patients (pts) from five Institutions treated with RT concomitant to TKI were retrospectively revised. Overall survival (OS) and toxicities were analyzed as endpoints of the study. RESULTS: Median age of pts was 65 years. TKIs were given for EGFR (81%)- or ALK (19%)-mutated metastatic NSCLC. Stereotactic RT (SRT) was delivered to 49 pts (46%). Patients with four or less metastasis were defined as oligometastatic/oligoprogressive (OM/OP); sites of RT were brain, bone, lung or others in 46%, 27%, 14% and 13%, respectively. Median OS was 23 months. At univariate analysis SRT, ECOG PS 0-1, OM/OP disease, lung sites and a TKI duration longer than median favorably affected OS (all p < 0.001). Multivariate analysis confirmed SRT (HR 0.355, CI 95% 0.212-0.595; p < 0.001) and median duration of TKI > 14 months (HR 0.17, 95% CI 0.10-0.30; p < 0.001) as independent factors related to better OS. Toxicities were rare. CONCLUSIONS: SRT seems to positively affect OS with limited toxicity in selected patients.

Pharmacology of Cardio-Oncology: Chronotropic and Lusitropic Effects of B-Type Natriuretic Peptide in Cancer Patients with Early Diastolic Dysfunction Induced by Anthracycline or Nonanthracycline Chemotherapy.

B-type natriuretic peptide (BNP) is widely used as a diagnostic marker of systolic dysfunction. We previously conducted a clinical study in which anthracycline or nonanthracycline chemotherapy did not cause systolic dysfunction in cancer patients; however, some patients showed asymptomatic alterations in diastolic relaxation, whereas others showed persistent elevations of BNP, measured as prohormone BNP amino-terminal fragment. Here we describe post hoc pharmacologic analyses showing that: 1) impaired relaxation and persistent elevations of BNP were mutually exclusive manifestations of diastolic dysfunction; 2) in some patients, BNP elevations were induced by an early compromise of myocardial relaxation; 3) BNP elevations then halted further deterioration of relaxation in a concentration-dependent manner; and 4) high BNP increased heart rate (HR). BNP elevations therefore caused positive lusitropy and chronotropism, which might be explained by activation of natriuretic receptor-associated guanylyl cyclase and production of cGMP in ventricular myocytes and sinoatrial node, respectively. BNP levels also influenced responses to a lusitropic drug, ranolazine, that was given to treat diastolic dysfunction. For patients with impaired relaxation and normal or only transiently high levels of BNP, ranolazine improved myocardial relaxation without inducing chronotropic effects. For patients in whom relaxation abnormalities were corrected by persistently high BNP levels, ranolazine substituted for BNP and decreased HR by diminishing BNP levels. These findings describe a pharmacologic scenario in which cancer drugs cause an early diastolic dysfunction that in some patients is both heralded and modulated by BNP elevations. Patients showing BNP elevations should therefore receive the adequate pharmacologic treatment of correcting diastolic dysfunction and tachycardia.

The Endogenous Lusitropic and Chronotropic Agent, B-Type Natriuretic Peptide, Limits Cardiac Troponin Release in Cancer Patients with an Early Impairment of Myocardial Relaxation Induced by Anthracyclines.

We have reported that cancer patients treated with anthracycline-based or nonanthracycline chemotherapy developed an early impairment of myocardial relaxation at echocardiography or persistent elevations of the cardiac hormone B-type natriuretic peptide (BNP). Post-hoc pharmacologic analyses showed that BNP elevations were induced by impaired relaxation and caused positive lusitropic effects that maintained normal relaxation. High BNP levels and impaired relaxation were therefore characterized as mutually exclusive manifestations of diastolic dysfunction, but high BNP levels resulted in positive chronotropism and inappropriate tachycardia. Some patients developed increased circulating levels of cardiac troponin I isoform (cTnI), a marker of cardiomyocyte necrosis. Here we have characterized whether cTnI elevations correlated with diastolic dysfunction that manifested as impaired relaxation or a high level of BNP. The effects of high BNP levels on cTnI elevations were also characterized. We show that impaired relaxation or high BNP levels were significantly more frequent in patients with cTnI elevations. High BNP levels diminished the plasma peak and area under the curve of cTnI, but this result was accompanied by inappropriate tachycardia. cTnI elevations occurred only in patients treated with anthracyclines; moreover, the association of impaired relaxation or high BNP levels with cTnI elevations was significantly more frequent in doxorubicin-treated patients compared with patients treated with its analog, epirubicin. These findings describe cause-and-effect relations between impaired relaxation and cardiomyocyte necrosis, illuminate the role of anthracycline analogs, denote that the beneficial effects of BNP in relieving impaired relaxation and cardiomyocyte necrosis are counterbalanced by inappropriate tachycardia. Patients showing troponin elevations and impaired relaxation or high BNP levels should be treated with lusitropic drugs that lack a positive chronotropism.

Radiotherapy and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors in Renal Cancer.

Treatment of metastatic renal cell carcinoma (mRCC) has seen substantial progress over the last decade. A number of targeted therapies have been shown to improve clinical outcome. Vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) are an effective option in treating mRCC. RCC is traditionally perceived to be a radioresistant malignancy with a limited role of radiotherapy (RT) in the management of localized disease. While RCC appears to be radioresistant using conventionally fractionated RT, preclinical data suggest increased radiosensitivity when an ablative, hypofractionated schedule is used. RT is a common treatment for metastases; therefore, it is important to understand how best to use the combination of RT with targeted therapies. Preclinical studies have suggested that the combination of anti-angiogenic drugs with RT enhances the therapeutic effect compared with ionizing radiation alone. However, clinical data gave rise to warnings due to an increased incidence of severe gastrointestinal side effects. This article reviews the literature behind the preclinical and clinical data of the combination of RT with VEGFR-TKIs currently approved for RCC (sunitinib, sorafenib, pazopanib, and axitinib), with a focus on dose schedules as well as efficacy and toxicity.

Early Diastolic Dysfunction after Cancer Chemotherapy: Primary Endpoint Results of a Multicenter Cardio-Oncology Study.

Asymptomatic diastolic dysfunction (DD) with preserved left ventricular ejection fraction (LVEF) is suspected to precede late cardiac events in cancer survivors treated by chemotherapy. We conducted the first multicenter study of early DD induced by chemotherapy. Patients who were candidates for standard dose chemotherapy were screened for the absence of cardiovascular risk factors, LVEF ≥50%, normal-for-age diastolic function at echocardiography (E/A ratio, E wave deceleration time; DT), normal levels of potential DD biomarkers like Nt-proBNP (≤125 pg/mL), and cardiac troponin I (cTnI, ≤0.05 ng/mL). Mitral Doppler (E/E') was left at the investigator's discretion. Chemotherapy-induced DD with preserved LVEF was diagnosed for patients showing LVEF ≥50% and any of the following: Nt-proBNP > 125 pg/mL, cTnI > 0.05 ng/mL, and out-of-range E/A and DT. Eighty patients (68 females, 12 males, median age 49 years) were evaluated at 1 week after chemotherapy (T1) [corrected]. Thirty-three protocol-defined diastolic events were observed (15 Nt-proBNP > 125 pg/mL, 14 grade I DD by E/A and DT, 4 cTnI > 0.05 ng/mL). The events occurred in 29 asymptomatic patients with LVEF ≥50% (36% incidence of DD with preserved LVEF). Interactions occurred between biomarkers and grade I DD. E/E' abnormalities were not observed. Both anthracycline-based and nonanthracycline regimens induced DD. These findings show that biomarkers and echocardiography intercept early DD in otherwise asymptomatic low-risk cancer patients treated by standard dose chemotherapy. These findings therefore call for the adequate cardiac management of cancer patients.

Radiation therapy in small cell lung cancer: a national Italian survey.

INTRODUCTION: Radiation therapy plays an important role in the management of SCLC both in curative and palliative setting, however, conflicting data from clinical trials incite debate over the appropriate use of radiation therapy regarding prophylactic cranial irradiation (PCI) and/or thoracic consolidative in extensive-stage SCLC (ES-SCLC). This survey is conducted to evaluate the current pattern of care among Italian radiation oncologists. METHODS: In June 2016, all Italian radiation oncologists were invited to a web-based survey. The survey contained 34 questions regarding the role of RT in SCLC. Questions pertaining the role of RT in the clinical management of both limited-stage (LS) and ES-SCLC were included. RESULTS: We received 48 responses from Italian radiation oncologists. More than half of respondents had been practicing for more than 10 years after completing residency training and 55% are subspecialists in lung cancer. Preferred management of LS-SCLC favored primary concurrent chemoradiotherapy (89%), even if the 36.9% usually delivered RT during or after the cycle 3 of chemotherapy, due to organizational issues. The most common dose and fractionation schedule in this setting was 60 Gy in 30 once-daily fractions. Furthermore, almost all respondents recommended PCI in patients with LS-SCLC. For ES-SCLC scenario, chemotherapy was defined the standard treatment by all respondents. PCI was recommended in ES-SCLC patients with thoracic complete remission (63% of respondents), with thoracic partial response (45%) and with thoracic stable disease (17%) after first-line chemotherapy. Lastly, the thoracic consolidative RT was recommended by 51% of respondents in patients with ES-SCLC in good response after first-line chemotherapy and a great variability was shown in clinical target volume definition, doses and fractionation schedules. CONCLUSIONS: Our analysis showed a high adherence to current guidelines among the respondents in regard to chemoradiation approach in LS-SCLC patients and to PCI indications and doses. The great variability in radiation therapy doses and volumes in the thoracic consolidative radiotherapy in ES-SCLC is concerning. Future clinical trials are needed to standardize these treatment approaches to improve treatment outcomes among patients with ES-SCLC.

Clinical Outcomes of Stereotactic Body Radiotherapy in Oligometastatic Gynecological Cancer.

OBJECTIVE: The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer. METHODS: The hospital records of 45 patients with F-fluorodeoxyglucose (F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen. RESULTS: Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.

Estimation of patient setup uncertainty using BrainLAB Exatrac X-Ray 6D system in image-guided radiotherapy.

The purpose of this study was to evaluate setup uncertainties for brain sites with ExacTrac X-Ray 6D system and to provide optimal margin guidelines. Fifteen patients with brain tumor were included in this study. Two X-ray images with ExacTrac X-Ray 6D system were used to verify patient position and tumor target localization before each treatment. The 6D fusion software first generates various sets of DRRs with position variations in both three translational and three rotational directions (six degrees of freedom) for the CT images. Setup variations (translation and rotation) after correction were recorded and corrected before treatment. The 3D deviations are expressed as mean ± standard deviation. The random error (Σ(σi)), systematic error (µi), and group systematic error (M(µi)) for the different X-ray were calculated using the definitions of van Herk.(1) Mean setup errors were calculated from X-ray images acquired after all fractions. There is moderate patient-to-patient variation in the vertical direction and small variations in systematic errors and magnitudes of random errors are smaller. The global systematic errors were measured to be less than 2.0 mm in each direction. Random component of all patients are smaller ranging from 0.1-0.3 mm small. The safety margin (SM) to the lateral, is 0.5 mm and 2.6 mm for van Herk(1) and Stroom et al.,(2) respectively, craniocaudal axis is 1.5 mm and 3.4 mm, respectively, and with respect to the antero-posterior axis, 2.3 mm and 3.9 mm. Daily X-ray imaging is essential to compare and assess the accuracy of treatment delivery to different anatomical locations.

Spinal metastases: From conventional fractionated radiotherapy to single-dose SBRT.

AIM: To review the recent evolution of spine SBRT with emphasis on single dose treatments. BACKGROUND: Radiation treatment of spine metastases represents a challenging problem in clinical oncology, because of the high risk of inflicting damage to the spinal cord. While conventional fractionated radiation therapy still constitutes the most commonly used modality for palliative treatment, notwithstanding its efficacy in terms of palliation of pain, local tumor control has been approximately 60%. This limited effectiveness is due to previous lack of technology to precisely target the tumor while avoiding the radiosensitive spinal cord, which constitutes a dose-limiting barrier to tumor cure. MATERIALS AND METHODS: A thorough review of the available literature on spine SBRT has been carried out and critically assessed. RESULTS: Stereotactic body radiotherapy (SBRT) emerges as an alternative, non-invasive high-precision approach, which allows escalation of tumor dose, while effectively sparing adjacent uninvolved organs at risk. Engaging technological advances, such as on-line Cone Beam Computed Tomography (CBCT), coupled with Dynamic Multi-Leaf Collimation (DMLC) and rapid intensity-modulated (IMRT) beam delivery, have promoted an interactive image-guided (IGRT) approach that precisely conforms treatment onto a defined target volume with a rapid dose fall-off to collateral non-target tissues, such as the spinal cord. Recent technological developments allow the use of the high-dose per fraction mode of hypofractionated SBRT for spinal oligometastatic cancer, even if only a few millimeters away from the tumor. CONCLUSION: Single-dose spine SBRT, now increasingly implemented, yields unprecedented outcomes of local tumor ablation and safety, provided that advanced technology is employed.