C. Deantoni

Higher-than-expected Severe (Grade 3–4) Late Urinary Toxicity After Postprostatectomy Hypofractionated Radiotherapy: A Single-institution Analysis of 1176 Patients

BACKGROUND Dose escalation and hypofractionation may have a role in postprostatectomy radiotherapy (RT), but at the risk of increasing urinary toxicity. OBJECTIVE To address predictors of severe (Grade ≥3) late urinary toxicities (LGUTOX3) after postoperative irradiation. DESIGN, SETTING, AND PARTICIPANTS A single-institution cohort of 1176 patients treated between 1993 and 2010 with adjuvant or salvage RT was analyzed. A total of 929 patients underwent conventionally fractionated (CF) RT (1.8 Gy per fraction; median dose to the prostatic bed: 70.2 Gy) with nonconformal RT (n=169), three-dimensional conformal RT (n=657), or intensity-modulated RT (n=103) technique, while 247 patients received hypofractionated helical TomoTherapy (median: 2.50 Gy per fraction) at the following doses: 117 patients at 65.8 Gy (2.35 Gy in 28 fractions), 80 patients at a median of 71.4 Gy (2.5-2.6 Gy in 28 fractions), and 50 patients at 58 Gy in 20 fractions. Total doses were converted into 2 Gy-equivalent doses (EQD2) following the linear quadratic model taking α/β=5. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable Cox regression models tested the relationship between clinicodosimetric variables and the risk of LGUTOX3 retrospectively, graded according to Common Terminology Criteria for Adverse Events v.4.0. RESULTS AND LIMITATIONS After a median follow-up of 98 mo, the 5-yr risk of LGUTOX3 was 6.9% and 18.1% in the CF and hypofractionated cohorts, respectively. At univariable analysis, the risk of LGUTOX3 was predicted by dose per fraction (hazard ratio [HR]: 2.96), acute Grade ≥2 toxicity (HR: 2.37), EQD2, pT4, and year of irradiation. At multivariable analyses, acute Grade ≥2 toxicity and dose per fraction independently predicted LGUTOX3 in the population, while an interaction analysis indicated a predictive role of hypertension in the hypofractionated cohort only. These findings are limited by their retrospective nature. CONCLUSIONS In the postprostatectomy setting, the logistic convenience of hypofractionation should be carefully balanced against the risk of severe late urinary sequelae. PATIENT SUMMARY This study investigated the causes of urinary adverse effects after postprostatectomy radiotherapy. Hypofractionation resulted in an increased risk of severe urinary toxicities.

Dose–volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation

PURPOSE To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. MATERIAL AND METHODS Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. RESULTS Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. CONCLUSIONS Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT.

11C-Choline PET/CT based Helical Tomotherapy as Treatment Approach for Bone Metastases in Recurrent Prostate Cancer Patients

BACKGROUND To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. METHODS This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CONCLUSION CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity.

PO-0749: Factors predicting late severe urinary incontinence after postprostatectomy RT: a longitudinal study

Results: Finally 550 patients with prostate cancer were included, with median age of 70 years old (47-85), Mean follow-up time was 136.8 months, between 5,6 and 245,8 months. D’Amico risk classification distribution was for low risk, mediun and high 20.4%, 36,5% and 43,1% respectively. RCI distribution categories was as follows 61,5%, 21,8 and 16,7%. Survival analysis showed significant differences (p<0.001) between RCI groups at 5 and 10 years. Survival probability was 98,2 and 88,5% ; 95% and 79,6% ; and 52,2% and 8,9% was respectively for each RCI category.

La radioterapia adiuvante nella cura del timoma

Il timoma e un tumore raro tuttavia nella popolazione adulta rappresenta la neoplasia piu comune del mediastino. La terapia del timoma prevede un approccio multidisciplinare ben definito per gli stadi iniziali, mentre la gestione dei pazienti in stadio avanzato e ancora controversa. Dal novembre 2002 al marzo 2010, 9 pazienti affetti da timoma sono stati curati con radioterapia adiuvante postoperatoria presso la SC di Radioterapia Oncologica della Fondazione IRCCS Policlinico San Matteo di Pavia. Tutti i pazienti sono stati curati con radioterapia conformazionale tridimensionale (3DCRT) sul mediastino, con una dose totale media di 52.6 Gy (range 50-56), frazionamento convenzionale (1.8-2 Gy/die per 5 giorni la settimana). Gli effetti collaterali acuti registrati sono stati: dermatite in 6 pazienti e disfagia in 8 pazienti. A circa due mesi dal termine della terapia tutti i pazienti presentavano risoluzione di tali effetti. Al dicembre 2011 con un follow-up medio di 50.1 mesi (range 16-102), mediana 37 mesi, tutti i pazienti risultavano liberi da malattia; 5 presentavano ancora sintomi relativi alla miastenia gravis. A distanza di tempo dalla radioterapia tutti i pazienti presentavano fibrosi polmonare di grado I nel volume irradiato, clinicamente non significativa ma rilevabile alla diagnostica per immagine (TC).

Un caso di carcinoma mammario maschile in stadio avanzato

Il carcinoma della mammella maschile e un tumore raro, rappresentando meno dell’1% di tutte le neoplasie mammarie, tuttavia la sua incidenza e in aumento. Sebbene la storia naturale e i fattori prognostici non differiscano dalle forme femminili, questa neoplasia si caratterizza per una maggiore mortalita in quanto i sintomi di esordio vengono spesso sottovalutati giungendo cosi alla diagnosi quando la malattia e gia in fase avanzata. Presentiamo il caso di un uomo di 53 anni affetto da carcinoma duttale infiltrante della mammella sinistra, curato con mastectomia radicale, chemioterapia, radioterapia ed ormonoterapia adiuvanti. L’intervallo di tempo libero da malattia e stato di 21 mesi; si e avuta successivamente progressione di malattia locoregionale e a distanza (comparsa di metastasi cutanee della parete toracica, ossee e pleuriche). Il paziente e deceduto a distanza di 56 mesi dalla diagnosi.

Chemioradioterapia nel carcinoma del pancreas localmente avanzato

Il carcinoma del pancreas e il secondo tumore piu frequente del tratto gastrointestinale ed e associato ad una prognosi infausta in quanto viene generalmente diagnosticato in stadio gia avanzato. La chemioradioterapia e in grado di influire sulla sopravvivenza prolungando l’intervallo di tempo libero da malattia e migliorando la resecabilita del tumore. Questo studio si e posto lo scopo di dimostrare l’efficacia e la tollerabilita della chemioterapia con Gemcitabina, seguita da radioterapia associata a somministrazione bisettimanale di basse dosi di Gemcitabina in pazienti affetti da adenocarcinoma del pancreas localmente avanzato, non metastatico. Sono stati curati 20 pazienti con diagnosi istologica di carcinoma pancreatico. Il follow-up medio e stato di 10 mesi (range 1-27); dopo la conclusione dello schema terapeutico 4 pazienti hanno raggiunto una stabilita locale di malattia, 7 pazienti sono andati incontro a progressione locale, e in 9 pazienti sono comparse metastasi a distanza. I disturbi maggiormente riscontrati durante il trattamento sono stati nausea e anoressia; il 25% dei pazienti non ha lamentato alcun effetto collaterale.

Radioterapia post-operatoria in pazienti con neoplasia localmente avanzata del distretto cervico-cefalico sottoposti a chirurgia demolitiva e ricostruzione con lembi: esperienza del gruppo oncologico testa-collo

The aim of this retrospective study was to evaluate the efficacy and acute and late toxicity of postoperative irradiation in patients affected by locally advanced head and neck cancer who underwent radical surgery with flap reconstruction. From January 2003 to January 2008, 27 patients affected by locally advanced head-neck cancer, treated with radical surgery with flap reconstruction, underwent 3D conformational radiotherapy. Twenty-three were males and 4 were females with mean age of 60.6 years (range 48-75 years). The cancer was placed in oral cavity in 12 patients (44.4%), in oropharynx in 2 patients (7.4%), in hypopharynx in 8 patients (29.6%) and in larynx in 5 patients (18.5%). All tumors were squamous. At staging we found T1N2b=3.7%, T2N0=11.1%, T2N1=11.1%, T2N2a=7.4%, T2N2b=3.7%, T2N2c=7.4%, T3N1=7.4%, T3N2b=11.1%, T3N2c=7.4%, T4aN0=7.4%, T4aN1=3.7%, T4aN2a=3.7%, T4aN2b=7.4%, T4aN2c=7.4%. The flaps were removed from radius (25.9%), pectoral (18.5%), forearm (14.8%), jejunum (14.8%), fibula (11.1%), thigh (11.1%) and platisma (3.7%). All patients were treated on surgical bed and bilateral cervical nodes (PTVII: 50-54 Gy). In 17 cases we defined also a PTVI (up to 66 Gy) on surgical bed if lips were infiltrated or on nodal seat if there was capsulary breaking. The dose was administered in fractions of 2 Gy for 5 days a week. At the end of treatment, all patients obtained completed remission of disease (CR). Out of totality of cases we observed disease free survival (DFS): 74.1% with medium follow up of 25.9 months, primary tumour relapse: 18.5%, nodal relapse: 2.7%, and distant metastases incidence: 2.7%. During treatment, G1-G2 mucositis, dermatitis, dysphagia, odynophagia, xerostomia, oedema and trismus were recorded but only two G3 events in 2 cases. All patients completed the treatment. No significant late toxicity was observed during the follow-up. None of the patients showed lips necrosis or pain. Few studies about flap reconstruction and postoperative irradiation are reported in literature. Our data show good results in terms of disease-free survival rate and very limited acute and late toxicity, especially in irradiated flaps.