Maurizio Valeriani

Fractionated stereotactic radiotherapy for skull base tumors: analysis of treatment accuracy using a stereotactic mask fixation system

BackgroundTo assess the accuracy of fractionated stereotactic radiotherapy (FSRT) using a stereotactic mask fixation system.Patients and MethodsSixteen patients treated with FSRT were involved in the study. A commercial stereotactic mask fixation system (BrainLAB AG) was used for patient immobilization. Serial CT scans obtained before and during FSRT were used to assess the accuracy of patient immobilization by comparing the isocenter position. Daily portal imaging were acquired to establish day to day patient position variation. Displacement errors along the different directions were calculated as combination of systematic and random errors.ResultsThe mean isocenter displacements based on localization and verification CT imaging were 0.1 mm (SD 0.3 mm) in the lateral direction, 0.1 mm (SD 0.4 mm) in the anteroposterior, and 0.3 mm (SD 0.4 mm) in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.4 mm), being maximum 1.4 mm. No significant differences were found during the treatment (P = 0.4). The overall isocenter displacement as calculated by 456 anterior and lateral portal images were 0.3 mm (SD 0.9 mm) in the mediolateral direction, -0.2 mm (SD 1 mm) in the anteroposterior direction, and 0.2 mm (SD 1.1 mm) in the craniocaudal direction. The largest displacement of 2.7 mm was seen in the cranio-caudal direction, with 95% of displacements < 2 mm in any direction.ConclusionsThe results indicate that the setup error of the presented mask system evaluated by CT verification scans and portal imaging are minimal. Reproducibility of the isocenter position is in the best range of positioning reproducibility reported for other stereotactic systems.

Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

PURPOSE Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. METHODS AND MATERIALS Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. RESULTS The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. CONCLUSIONS Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized studies are needed to compare HypoRT to conventional treatment.

Clinical Outcomes of Single Dose Stereotactic Radiotherapy for Lung Metastases

INTRODUCTION Stereotactic body radiation therapy is an emerging noninvasive technique for the treatment of oligometastatic cancer. The use of small numbers of large doses achieve a high percentage of local control. The aim of this study was to evaluate the efficacy and tolerability of SBRT for the treatment of lung metastases in a cohort of patients treated between 2008 and 2012 at our institution. PATIENTS AND METHODS A total of 66 patients with oligometastatic lung tumors (single pulmonary nodules in 40 patients; 61%) were included in the study. SBRT was performed with a stereotactic body frame and a 3-D conformal technique. Forty-nine central tumors received 23 Gy in a single fraction and 54 peripheral tumors received a dose of 30 Gy in a single fraction. The primary end point was local control; secondary end points were survival and toxicity. RESULTS Median follow-up was 15 months (range, 3-45 months). Local control rates at 1 and 2 years were 89.1% and 82.1%, overall survival rates were 76.4% and 31.2%, cancer-specific survival rates were 78.5% and 35.4%, and progression-free survival rates were 53.9% and 22%, respectively. Median survival time was 12 months, and median progression-free survival time was 10 months. Toxicity profiles were good, with 2 cases of Grade 3 toxicity (pneumonitis). CONCLUSION SBRT is an effective and safe local treatment option for patients with lung metastases, although it remains investigational; longer follow-up to confirm results is required.

BRACHYTHERAPY FOR SQUAMOUS CELL CARCINOMA OF THE LIP. THE EXPERIENCE OF THE INSTITUTE OF RADIOLOGY OF THE UNIVERSITY OF ROME LA SAPIENZA

Aims and background Cancer of the lip is the most common malignancy occurring in the oral cavity. The aim of our retrospective study was to review the results of patients with lower lip squamous cell carcinoma who were treated with radiotherapy. Methods & study design From 1970 to 1992, 57 patients with squamous cell carcinoma of the lower lip were treated at the Institute of Radiology of the University of Rome “La Sapienza” with low-dose rate interstitial brachytherapy. According to the UICC 1992 TNM classification, the disease stage was T1 in 27 (47%) cases, T2 in 20 (35%) and T3 in 10 (18%); 8 patients (14%) were cN+. The median tumor dose was 62 Gy (range, 44-96): 10 patients (18%) received a total dose < 50 Gy, 28 (49%) between 50 and 70 Gy, and 19 (33%) > 70 Gy. The cN+ cases were irradiated to total doses of 65-70 Gy on the involved station. Ail patients obtained complete remission. Results The actuarial overall survival rates at 3, 5 and 10 years were 95%, 76% and 53%; actuarial disease-free survival at 3, 5 and 10 years was 84%, 81%, and 81%, respectively. Actuarial cause-specific survival was 98%, 88% and 84% at 3, 5 and 10 years, respectively. Actuarial local control rate was 90% at 3 and 5 years, rising to 94% with salvage surgery. Local-regional control was obtained in 90% and 86% of patients at 3 and 5 years, and in 93% and 89% of cases, respectively, following surgery. Five of 11 deaths were due to local-regional or distant disease recurrence. Conclusions Tumor stage and positivity of regional nodes were the only predictive factors of survival and disease control. Radiation-induced morbidity was very low, and all patients considered their cosmetic outcome at least satisfactory.

Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: Is it better than three dimensional conformal radiotherapy?

BackgroundCure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients.MethodsTen HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints.ResultsRegarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs.ConclusionsIn HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

Neoadjuvant chemoradiation for locally advanced carcinoma of the rectum.

Aims and background The aim of this paper is to confirm the efficacy to reduce incidence of relapses, to increase rates of conservative radical surgery and eventually survival of concomitant neo-adjuvant chemo-radiotherapy. Methods From January 1992 to October 1999, 140 stage II (50.7%) and III (49.3%) patients with adenocarcinoma of the rectum were treated with concomitant chemoradiotherapy followed by radical surgery. Treatment consisted of 25 fractions of 180 cGy (5 days per week), for a total dose of 45 Gy on the whole pelvis. Chemotherapy consisted of 5-FU (350 mg/m2) and leucoverin (10 mg/m2) in bolus for 5 days on days 1-5 and 29-33 of radiation. After an interval of 4-6 weeks, all patients were submitted to surgery. Results The median follow-up was 48 months (median, 1-97). At 5 years the overall survival was 71.3% and relapse-free survival was 79.4%. The rate of local control was 90%. Twenty-two (15.7%) patients developed distant metastases. All patients underwent surgery: 26 (18.6%) local excision, 79 (56.4%) anterior resection, 33 (23.6%) abdomino-perineal resection, and 2 (1.4%) Hartmann resection. Consequently, 107 cases (75.4%) underwent conservative surgery. At the time of surgery, 34 patients had negative specimens (24.3%), 45 were in stage I (32.2%), 31 in stage II (22.1%), 32 in stage III (21.4%). The incidence of any grade 3 acute toxicity (WHO) was 5% diarrhea, 20% tenesmus and 11.4% myelosuppression. Conclusions The results of this study confirm good tolerance, minor surgery-related complications and efficacy of this regimen on local and distant disease control, with a high percentage of sphincter-saving surgery.

Late morbidity and oncological outcome after radical hypofractionated radiotherapy in men with prostate cancer

Study Type – Therapy (case control)
Level of Evidence 3b

Radiation therapy after breast reconstruction: outcomes, complications, and patient satisfaction

PurposeThe aim of this study was to evaluate treatmentrelated complications, outcomes, and patient satisfaction in women with locally advanced breast cancer who received post-mastectomy radiation therapy (PMRT) after breast reconstruction (BR).Materials and methodsBetween October 2007 and November 2010, 46 patients with locally advanced breast cancer who underwent mastectomy followed by BR received PMRT at our Department. Radiotherapy was delivered to the chest wall with a dose of 50 Gy in 25 fractions over 5 weeks.ResultsThe median follow-up was 19 months. Skin erythema grade 1 and 2 was seen in 44 (96%) and two (4%) patients, respectively. Major complications, requiring additional corrective surgical procedure, occurred in three (7%) patients (one patient with prosthesis, one patient with tissue expander and one patient with deep inferior epigastric perforator flap). At univariate analysis, smoking, chemotherapy, hormone therapy with tamoxifen and reconstruction with implant were associated with overall complications (capsular contracture and reconstruction failure). Forty (86%) patients were very satisfied or satisfied with the cosmetic outcome of reconstruction.ConclusionsRadiotherapy can be safely delivered after BR, with a low complication rate and good patient satisfaction. Further randomised studies are needed to better define the optimal timing of breast reconstruction and post-mastectomy radiation therapy.RiassuntoObiettivoScopo del nostro lavoro è stato valutare le complicanze del trattamento e il livello di soddisfazione del risultato in pazienti con tumore della mammella localmente avanzato sottoposte a trattamento radioterapico post-mastectomia e ricostruzione mammaria.Materiali e metodiTra ottobre 2007 e novembre 2010, presso il nostro Dipartimento, 46 pazienti affette da neoplasia della mammella sono state sottoposte a trattamento radioterapico dopo intervento di mastectomia radicale e ricostruzione mammaria. La dose totale somministrata sulla parete toracica è stata di 50 Gy in 25 frazioni.RisultatiA un follow-up mediano di 19 mesi, si è osservata la comparsa di eritema cutaneo di grado 1 e 2 rispettivamente in 44 (96%) e in 2 (4%) pazienti. Complicanze maggiori, che hanno richiesto un ulteriore intervento chirurgico correttivo, sono state osservate in 3 pazienti (7%). All’analisi univariata il fumo, la chemioterapia, il tamoxifene e la ricostruzione con protesi risultano associate a un maggior rischio di complicanze generali (contrattura capsulare e fallimento della ricostruzione). Quaranta pazienti (86%) si sono mostrate soddisfatte o molto soddisfatte dei risultati estetici.ConclusioniLa radioterapia dopo ricostruzione mammaria è un trattamento sicuro associato a una bassa incidenza di complicanze e a un buon livello di soddisfazione da parte delle pazienti. Sono necessari ulteriori studi per definire meglio la sequenza ottimale di trattamento tra ricostruzione mammaria e radioterapia.

Acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with concurrent cetuximab and radiotherapy

PurposeThe authors report acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with radiotherapy and cetuximab.Materials and methodsData collection was performed prospectively on patients treated from September 2007 to March 2009. Treatment consisted of 64.8–70 Gy radiotherapy in conventional fractions and cetuximab.ResultsTwo out of 14 patients did not complete the planned combined treatment; radiotherapy was temporarily suspended in six other patients. Seven of 12 patients received cetuximab until the end of radiotherapy. Treatment breaks were principally due to severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients and G3-4 mucous toxicity in seven (50%). One patient died of sepsis.ConclusionsIn our experience, severe acute toxic reactions are common in patients treated with radiotherapy and concurrent cetuximab, resulting in frequent breaks or incomplete treatment with potential reduction in disease control.RiassuntoObiettivoScopo del nostro lavoro è stato riportare i dati relativi alla tossicità acuta in 14 pazienti affetti da carcinoma squamoso localmente avanzato del distretto testa-collo trattati con radioterapia e cetuximab in contemporanea.Materiali e metodiLa raccolta dei dati è stata effettuata in modo prospettico relativamente ai pazienti trattati da settembre 2007 a marzo 2009. Lo schema di trattamento consisteva nella radioterapia per una dose totale di 64,8–70 Gy con frazionamento convenzionale associata al cetuximab.RisultatiIn 2 dei 14 pazienti il trattamento combinato pianificato non è stato completato; la radioterapia è stata temporaneamente interrotta in altri 6 pazienti. In 7 dei 12 pazienti che hanno ricevuto la terapia combinata il cetuximab è stato somministrato fino al termine della radioterapia. Le interruzioni sono state principalmente imputabili all’insorgenza di tossicità cutanea o mucosa severa. In tutti i pazienti è comparso rash cutaneo di tipo acneiforme; tossicità cutanea di grado 3–4 si è verificata in 5 (36%) pazienti mentre tossicità mucosa di grado 3–4 si è avuta in 7 (50%) pazienti; un paziente è deceduto per sepsi.ConclusioniNella nostra esperienza gli effetti tossici acuti di entità severa nei pazienti trattati con radioterapia e cetuximab concomitante sono stati comuni implicando interruzioni frequenti della terapia o l’impossibilità di completare il trattamento con potenziale minor efficacia sul controllo della malattia.