Roberta Muni

Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma

OBJECTIVES The optimal treatment for patients with glioblastoma with unfavorable prognostic factors, such as old age and low performance status, remains controversial. We conducted a prospective study to assess the effect of temozolomide and short-course radiation versus short-course radiation alone in the treatment of poor-prognosis patients with newly diagnosed glioblastoma. PATIENTS AND METHODS Forty-five patients with a newly diagnosed glioblastoma, older than 70 years or aged 50-70 years and with a Karnofsky performance score <or=70 were enrolled in this prospective study. Twenty-three patients were treated with an abbreviated course of radiotherapy (30 Gy in 6 fractions over 2 weeks) and 22 patients with the same radiotherapy schedule plus adjuvant temozolomide at the dose of 150-200 mg/m(2) for 5 days every 28-day cycle. The primary end point was overall survival. Secondary end points included progression-free survival and toxicity. RESULTS Median overall survival was 7.3 months in the radiotherapy group and 9.4 months in the radiotherapy plus temozolomide group (P = 0.003), with respective 6-month overall survivals of 78% and 95%, respectively. Median progression-free survival was 4.4 months in the radiotherapy group and 5.5 months in the radiotherapy plus temozolomide group (P = 0.01), and respective 6-month progression-free survival rates were 22% and 45%. In multivariate analysis, Karnofsky performance score was the only significant independent predictive factor of survival (P = 0.03). Adverse effects of radiotherapy were mainly represented by neurotoxicity (24%), which resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 36% of patients treated with temozolomide. CONCLUSIONS The addition of temozolomide to short-term radiotherapy resulted in a statistically significant survival benefit with minimal additional toxicity in poor-prognosis patients with newly diagnosed glioblastoma. Future studies need to define the best combined regimens of radiotherapy and temozolomide on survival and quality of life in this subgroup of patients.

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.

A new nomogram for estimating survival in patients with brain metastases secondary to colorectal cancer

BACKGROUND The prognosis of brain metastases (BM) in colorectal cancer (CRC) is extremely poor, but the incidence is increasing. The performance of existing prognostic classifications such as recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) has never been evaluated in this specific setting. Moreover, the development of nomograms for estimating survival in such patients could be extremely helpful for treating physicians. PATIENTS AND METHODS Between 2000 and 2013, data from 227 patients with BM from CRC were collected at 8 Italian institutions. Overall survival (OS) was estimated with the Kaplan-Meier method and statistical comparison between curves was performed using the log-rank test. The discriminative ability for OS of RPA and GPA was assessed by the Harrell C-index from univariable Cox models. Putative prognostic factors for OS were also studied by multivariable Cox analysis, using the Harrell C index to evaluate the model discriminative ability. After a backward variable selection, a nomogram was developed to predict median survival time from individual patient- and tumor-related characteristics. The nomogram was externally validated on an independent series. RESULTS After a median follow-up of 59 months, fifty percent of patients were still at risk at 5 months. The C index was 0.594 and 0.607 for the RPA and GPA classifications, respectively. The C-index associated with the final multivariable Cox model used for developing the nomogram was 0.643; the favorable prognostic factors for survival were lower age (p=0.061), better Karnofsky performance status (p<0.001), supratentorial site of BM (p<0.001), and lower number of BM (p=0.035). The C index evaluated on the validation series was 0.733, even better than in the development series; also, the calibration of nomogram predictions was good. CONCLUSION The C-index associated to the nomogram model was slightly higher than that obtained for the RPA and GPA classifications. Most importantly, the very satisfactory results of nomogram validation on the external series, make us confident that our instrument may assist in prognostic assessment, treatment decision making, and enrollment into clinical trials.

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.